Infectious Diseases

The Centers for Disease Control and Prevention is warning of an early surge in respiratory disease caused by multiple viruses. As influenza viruses, respiratory syncytial virus (RSV), SARS-CoV-2, and rhinovirus/enterovirus simultaneously circulate, the agency cautioned that this confluence of viral activity could strain the health care system, according to a CDC Health Network Alert advisory issued Nov. 4.

“This early increase in disease incidence highlights the importance of optimizing respiratory virus prevention and treatment measures, including prompt vaccination and antiviral treatment,” the alert stated.

The CDC reports that RSV activity is increasing nationally, but in some areas – such as the South and Mountain West – cases appear to be trending downward.

Influenza cases continue to climb, with the virus activity being the highest in the South, Mid-Atlantic, and the south-central West Coast, according to CDC data. “In fact, we’re seeing the highest influenza hospitalization rates going back a decade,” said José Romero, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases, during a press briefing. The agency estimates that there have been 1.6 million illnesses, 13,000 hospitalizations, and 730 deaths from the flu so far this season. As of Nov. 4, there have been two pediatric deaths.

COVID-19 cases appear to have plateaued in the past three weeks, Dr. Romero said; however, the CDC expects that there will be “high-level circulation of SARS-CoV-2 this fall and winter,” the health alert stated.

The CDC advised that all eligible individuals aged 6-months or older should be vaccinated against COVID-19 and influenza. To protect against RSV-hospitalization, high-risk children should receive the monoclonal antibody drug palivizumab (Synagis). High-risk children include infants born before 29 weeks, children younger than age 2 with chronic lung disease or hemodynamically significant congenital heart disease, and children with suppressed immune systems or neuromuscular disorders.

Any patient with confirmed or suspected flu who is hospitalized, at higher risk for influenza complications, or who has a severe or progressive illness should be treated as early as possible with antivirals, such as oral oseltamivir (Tamiflu).

Patients with confirmed SARS-CoV-2 infection with increased risk of complications should also be treated with antivirals, such as nirmatrelvir and ritonavir (Paxlovid) or remdesivir (Veklury).

Patients should also be reminded to wash their hands frequently, cover coughs and sneezes, stay home when sick, and avoid close contact with people who are sick, the CDC advised.

“There’s no doubt that we will face some challenges this winter,” said Dawn O’Connell, HHS Assistant Secretary for Preparedness and Response, “but it’s important to remember that RSV and flu are not new, and we have safe and effective vaccines for COVID-19 and the flu.”

A version of this article first appeared on Medscape.com.

The Centers for Disease Control and Prevention is warning of an early surge in respiratory disease caused by multiple viruses. As influenza viruses, respiratory syncytial virus (RSV), SARS-CoV-2, and rhinovirus/enterovirus simultaneously circulate, the agency cautioned that this confluence of viral activity could strain the health care system, according to a CDC Health Network Alert advisory issued Nov. 4.

“This early increase in disease incidence highlights the importance of optimizing respiratory virus prevention and treatment measures, including prompt vaccination and antiviral treatment,” the alert stated.

The CDC reports that RSV activity is increasing nationally, but in some areas – such as the South and Mountain West – cases appear to be trending downward.

Influenza cases continue to climb, with the virus activity being the highest in the South, Mid-Atlantic, and the south-central West Coast, according to CDC data. “In fact, we’re seeing the highest influenza hospitalization rates going back a decade,” said José Romero, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases, during a press briefing. The agency estimates that there have been 1.6 million illnesses, 13,000 hospitalizations, and 730 deaths from the flu so far this season. As of Nov. 4, there have been two pediatric deaths.

COVID-19 cases appear to have plateaued in the past three weeks, Dr. Romero said; however, the CDC expects that there will be “high-level circulation of SARS-CoV-2 this fall and winter,” the health alert stated.

The CDC advised that all eligible individuals aged 6-months or older should be vaccinated against COVID-19 and influenza. To protect against RSV-hospitalization, high-risk children should receive the monoclonal antibody drug palivizumab (Synagis). High-risk children include infants born before 29 weeks, children younger than age 2 with chronic lung disease or hemodynamically significant congenital heart disease, and children with suppressed immune systems or neuromuscular disorders.

Any patient with confirmed or suspected flu who is hospitalized, at higher risk for influenza complications, or who has a severe or progressive illness should be treated as early as possible with antivirals, such as oral oseltamivir (Tamiflu).

Patients with confirmed SARS-CoV-2 infection with increased risk of complications should also be treated with antivirals, such as nirmatrelvir and ritonavir (Paxlovid) or remdesivir (Veklury).

Patients should also be reminded to wash their hands frequently, cover coughs and sneezes, stay home when sick, and avoid close contact with people who are sick, the CDC advised.

“There’s no doubt that we will face some challenges this winter,” said Dawn O’Connell, HHS Assistant Secretary for Preparedness and Response, “but it’s important to remember that RSV and flu are not new, and we have safe and effective vaccines for COVID-19 and the flu.”

A version of this article first appeared on Medscape.com.

The Centers for Disease Control and Prevention is warning of an early surge in respiratory disease caused by multiple viruses. As influenza viruses, respiratory syncytial virus (RSV), SARS-CoV-2, and rhinovirus/enterovirus simultaneously circulate, the agency cautioned that this confluence of viral activity could strain the health care system, according to a CDC Health Network Alert advisory issued Nov. 4.

“This early increase in disease incidence highlights the importance of optimizing respiratory virus prevention and treatment measures, including prompt vaccination and antiviral treatment,” the alert stated.

The CDC reports that RSV activity is increasing nationally, but in some areas – such as the South and Mountain West – cases appear to be trending downward.

Influenza cases continue to climb, with the virus activity being the highest in the South, Mid-Atlantic, and the south-central West Coast, according to CDC data. “In fact, we’re seeing the highest influenza hospitalization rates going back a decade,” said José Romero, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases, during a press briefing. The agency estimates that there have been 1.6 million illnesses, 13,000 hospitalizations, and 730 deaths from the flu so far this season. As of Nov. 4, there have been two pediatric deaths.

COVID-19 cases appear to have plateaued in the past three weeks, Dr. Romero said; however, the CDC expects that there will be “high-level circulation of SARS-CoV-2 this fall and winter,” the health alert stated.

The CDC advised that all eligible individuals aged 6-months or older should be vaccinated against COVID-19 and influenza. To protect against RSV-hospitalization, high-risk children should receive the monoclonal antibody drug palivizumab (Synagis). High-risk children include infants born before 29 weeks, children younger than age 2 with chronic lung disease or hemodynamically significant congenital heart disease, and children with suppressed immune systems or neuromuscular disorders.

Any patient with confirmed or suspected flu who is hospitalized, at higher risk for influenza complications, or who has a severe or progressive illness should be treated as early as possible with antivirals, such as oral oseltamivir (Tamiflu).

Patients with confirmed SARS-CoV-2 infection with increased risk of complications should also be treated with antivirals, such as nirmatrelvir and ritonavir (Paxlovid) or remdesivir (Veklury).

Patients should also be reminded to wash their hands frequently, cover coughs and sneezes, stay home when sick, and avoid close contact with people who are sick, the CDC advised.

“There’s no doubt that we will face some challenges this winter,” said Dawn O’Connell, HHS Assistant Secretary for Preparedness and Response, “but it’s important to remember that RSV and flu are not new, and we have safe and effective vaccines for COVID-19 and the flu.”

A version of this article first appeared on Medscape.com.

A man in England who was infected with an early strain of COVID-19 was finally cleared 411 days after first testing positive, according to experts in the United Kingdom. 

The man was treated with a mixture of neutralizing monoclonal antibodies, King’s College London said in a news release.

The man, 59, tested positive in December 2020 and tested negative in January 2022. He had a weakened immune system because of a previous kidney transplant. He received three doses of vaccine and his symptoms lessened, but he kept testing positive for COVID.

To find out if the man had a persistent infection or had been infected several times, doctors did a genetic analysis of the virus.

“This revealed that the patient’s infection was a persistent infection with an early COVID variant – a variation of the original Wuhan variant that was dominant in the United Kingdom in the later months of 2020. Analysis found the patient’s virus had multiple mutations since he was first infected,” King’s College said.

The doctors treated him with a Regeneron treatment that is no longer widely used because it’s not effective against newer COVID variants.

“Some new variants of the virus are resistant to all the antibody treatments available in the United Kingdom and Europe. Some people with weakened immune systems are still at risk of severe illness and becoming persistently infected. We are still working to understand the best way to protect and treat them,” Luke Snell, MD, from the King’s College School of Immunology & Microbial Sciences, said in the news release.

This is one of the longest known cases of COVID infection. Another man in England was infected with COVID for 505 days before his death, which King’s College said was the longest known COVID infection.

A version of this article first appeared on WebMD.com.

A man in England who was infected with an early strain of COVID-19 was finally cleared 411 days after first testing positive, according to experts in the United Kingdom. 

The man was treated with a mixture of neutralizing monoclonal antibodies, King’s College London said in a news release.

The man, 59, tested positive in December 2020 and tested negative in January 2022. He had a weakened immune system because of a previous kidney transplant. He received three doses of vaccine and his symptoms lessened, but he kept testing positive for COVID.

To find out if the man had a persistent infection or had been infected several times, doctors did a genetic analysis of the virus.

“This revealed that the patient’s infection was a persistent infection with an early COVID variant – a variation of the original Wuhan variant that was dominant in the United Kingdom in the later months of 2020. Analysis found the patient’s virus had multiple mutations since he was first infected,” King’s College said.

The doctors treated him with a Regeneron treatment that is no longer widely used because it’s not effective against newer COVID variants.

“Some new variants of the virus are resistant to all the antibody treatments available in the United Kingdom and Europe. Some people with weakened immune systems are still at risk of severe illness and becoming persistently infected. We are still working to understand the best way to protect and treat them,” Luke Snell, MD, from the King’s College School of Immunology & Microbial Sciences, said in the news release.

This is one of the longest known cases of COVID infection. Another man in England was infected with COVID for 505 days before his death, which King’s College said was the longest known COVID infection.

A version of this article first appeared on WebMD.com.

A man in England who was infected with an early strain of COVID-19 was finally cleared 411 days after first testing positive, according to experts in the United Kingdom. 

The man was treated with a mixture of neutralizing monoclonal antibodies, King’s College London said in a news release.

The man, 59, tested positive in December 2020 and tested negative in January 2022. He had a weakened immune system because of a previous kidney transplant. He received three doses of vaccine and his symptoms lessened, but he kept testing positive for COVID.

To find out if the man had a persistent infection or had been infected several times, doctors did a genetic analysis of the virus.

“This revealed that the patient’s infection was a persistent infection with an early COVID variant – a variation of the original Wuhan variant that was dominant in the United Kingdom in the later months of 2020. Analysis found the patient’s virus had multiple mutations since he was first infected,” King’s College said.

The doctors treated him with a Regeneron treatment that is no longer widely used because it’s not effective against newer COVID variants.

“Some new variants of the virus are resistant to all the antibody treatments available in the United Kingdom and Europe. Some people with weakened immune systems are still at risk of severe illness and becoming persistently infected. We are still working to understand the best way to protect and treat them,” Luke Snell, MD, from the King’s College School of Immunology & Microbial Sciences, said in the news release.

This is one of the longest known cases of COVID infection. Another man in England was infected with COVID for 505 days before his death, which King’s College said was the longest known COVID infection.

A version of this article first appeared on WebMD.com.

The COVID-19 bivalent Pfizer/BioNTech vaccine triggers a stronger immune response than a fourth dose of the original vaccine, the company reported on Nov. 4, supporting calls by public health officials for eligible people to get this booster before a potential COVID-19 surge this winter.

The company’s ongoing phase 2/3 study of their Omicron BA.4 and BA.5 bivalent – which targets both the virus’ original strain and the two subvariants – shows that the vaccine offered the strongest protection in people older than 55 years.

One month after receiving a 30-mcg booster with the bivalent vaccine, those older than 55 had four times more neutralizing antibodies against these Omicron subvariants, compared with people who received the original monovalent vaccine as a booster in the study.

Researchers compared the geometric mean titer (GMT) levels of these antibodies in three groups before and 1 month after boosting. The 36 people older than 55 years in the released study findings had an GMT level of 896 with the bivalent booster, a level 13 times higher than before this immunization.

For the 38 adults ages 18-55 in the study, the GMT level increased to 606 at 1 month after the bivalent booster, an increase of almost 10-fold, compared with baseline. In a comparator group of 40 people receiving the original vaccine as a fourth dose, the GMT level was 236, or threefold higher than before their booster shot.

The newly released data is “very encouraging and consistent now with three studies all showing a substantial 3-4 fold increased level of neutralizing antibodies versus BA.5 as compared with the original booster,” said Eric Topol, MD, director of the Scripps Research Translational Institute in La Jolla, Calif., and editor-in-chief of Medscape Medical News.

Pfizer and BioNTech announced the updated findings in a Nov. 4 press release.

A booster dose of the BA.4/BA.5-adapted bivalent vaccine is authorized for emergency use by the Food and Drug Administration for ages 5 years and older. The safety and tolerability profile of the Pfizer/BioNTech bivalent booster remains favorable and similar to the original COVID-19 vaccine, the company reported.

Until recently, the BA.5 Omicron variant was the dominant strain in the United States, but is now getting elbowed out by the subvariants BQ.1.1, BQ.1, and BA.4.6, which together make up almost 45% of the circulating virus.
 

Some skepticism

“It is important to note that these data are press-release level, which does not allow a view of the data totality,” Hana El Sahly, MD, professor of molecular virology and microbiology, Baylor College of Medicine, Houston, said in an interview.

“For example, there may be significant differences between the groups, and the release mentions at least one difference that is of importance: the interval since the last vaccination which often affects the response to subsequent boosting,” she said.

Dr. El Sahly added that the findings are not surprising. “In the short term, a variant-specific vaccine produces a higher level of antibody against the variant in the vaccine than the vaccines based on the ancestral strains.”

More researcher results are warranted. “These data do not indicate that these differences between the two vaccines translate into a meaningful clinical benefit at a population level,” Dr. El Sahly said.
 

An uncertain winter ahead

“As we head into the holiday season, we hope these updated data will encourage people to seek out a COVID-19 bivalent booster as soon as they are eligible in order to maintain high levels of protection against the widely circulating Omicron BA.4 and BA.5 sublineages,” Albert Bourla, Pfizer chairman and CEO, stated in the release.

The updated data from the Pfizer/BioNTech study are “all the more reason to get a booster, with added protection also versus BQ.1.1, which will soon become dominant in the U.S.,” Dr. Topol predicted.

It is unclear when the next surge will happen, as COVID-19 does not always follow a seasonal pattern, at least not yet, Dr. El Sahly said. “Regardless, it is reasonable to recommend additional vaccine doses to immunocompromised and frail or older persons. More importantly, influenza vaccination and being up to date on pneumococcal vaccines are highly recommended as soon as feasible, given the early and intense flu season.”

A version of this article first appeared on Medscape.com.

The COVID-19 bivalent Pfizer/BioNTech vaccine triggers a stronger immune response than a fourth dose of the original vaccine, the company reported on Nov. 4, supporting calls by public health officials for eligible people to get this booster before a potential COVID-19 surge this winter.

The company’s ongoing phase 2/3 study of their Omicron BA.4 and BA.5 bivalent – which targets both the virus’ original strain and the two subvariants – shows that the vaccine offered the strongest protection in people older than 55 years.

One month after receiving a 30-mcg booster with the bivalent vaccine, those older than 55 had four times more neutralizing antibodies against these Omicron subvariants, compared with people who received the original monovalent vaccine as a booster in the study.

Researchers compared the geometric mean titer (GMT) levels of these antibodies in three groups before and 1 month after boosting. The 36 people older than 55 years in the released study findings had an GMT level of 896 with the bivalent booster, a level 13 times higher than before this immunization.

For the 38 adults ages 18-55 in the study, the GMT level increased to 606 at 1 month after the bivalent booster, an increase of almost 10-fold, compared with baseline. In a comparator group of 40 people receiving the original vaccine as a fourth dose, the GMT level was 236, or threefold higher than before their booster shot.

The newly released data is “very encouraging and consistent now with three studies all showing a substantial 3-4 fold increased level of neutralizing antibodies versus BA.5 as compared with the original booster,” said Eric Topol, MD, director of the Scripps Research Translational Institute in La Jolla, Calif., and editor-in-chief of Medscape Medical News.

Pfizer and BioNTech announced the updated findings in a Nov. 4 press release.

A booster dose of the BA.4/BA.5-adapted bivalent vaccine is authorized for emergency use by the Food and Drug Administration for ages 5 years and older. The safety and tolerability profile of the Pfizer/BioNTech bivalent booster remains favorable and similar to the original COVID-19 vaccine, the company reported.

Until recently, the BA.5 Omicron variant was the dominant strain in the United States, but is now getting elbowed out by the subvariants BQ.1.1, BQ.1, and BA.4.6, which together make up almost 45% of the circulating virus.
 

Some skepticism

“It is important to note that these data are press-release level, which does not allow a view of the data totality,” Hana El Sahly, MD, professor of molecular virology and microbiology, Baylor College of Medicine, Houston, said in an interview.

“For example, there may be significant differences between the groups, and the release mentions at least one difference that is of importance: the interval since the last vaccination which often affects the response to subsequent boosting,” she said.

Dr. El Sahly added that the findings are not surprising. “In the short term, a variant-specific vaccine produces a higher level of antibody against the variant in the vaccine than the vaccines based on the ancestral strains.”

More researcher results are warranted. “These data do not indicate that these differences between the two vaccines translate into a meaningful clinical benefit at a population level,” Dr. El Sahly said.
 

An uncertain winter ahead

“As we head into the holiday season, we hope these updated data will encourage people to seek out a COVID-19 bivalent booster as soon as they are eligible in order to maintain high levels of protection against the widely circulating Omicron BA.4 and BA.5 sublineages,” Albert Bourla, Pfizer chairman and CEO, stated in the release.

The updated data from the Pfizer/BioNTech study are “all the more reason to get a booster, with added protection also versus BQ.1.1, which will soon become dominant in the U.S.,” Dr. Topol predicted.

It is unclear when the next surge will happen, as COVID-19 does not always follow a seasonal pattern, at least not yet, Dr. El Sahly said. “Regardless, it is reasonable to recommend additional vaccine doses to immunocompromised and frail or older persons. More importantly, influenza vaccination and being up to date on pneumococcal vaccines are highly recommended as soon as feasible, given the early and intense flu season.”

A version of this article first appeared on Medscape.com.

The COVID-19 bivalent Pfizer/BioNTech vaccine triggers a stronger immune response than a fourth dose of the original vaccine, the company reported on Nov. 4, supporting calls by public health officials for eligible people to get this booster before a potential COVID-19 surge this winter.

The company’s ongoing phase 2/3 study of their Omicron BA.4 and BA.5 bivalent – which targets both the virus’ original strain and the two subvariants – shows that the vaccine offered the strongest protection in people older than 55 years.

One month after receiving a 30-mcg booster with the bivalent vaccine, those older than 55 had four times more neutralizing antibodies against these Omicron subvariants, compared with people who received the original monovalent vaccine as a booster in the study.

Researchers compared the geometric mean titer (GMT) levels of these antibodies in three groups before and 1 month after boosting. The 36 people older than 55 years in the released study findings had an GMT level of 896 with the bivalent booster, a level 13 times higher than before this immunization.

For the 38 adults ages 18-55 in the study, the GMT level increased to 606 at 1 month after the bivalent booster, an increase of almost 10-fold, compared with baseline. In a comparator group of 40 people receiving the original vaccine as a fourth dose, the GMT level was 236, or threefold higher than before their booster shot.

The newly released data is “very encouraging and consistent now with three studies all showing a substantial 3-4 fold increased level of neutralizing antibodies versus BA.5 as compared with the original booster,” said Eric Topol, MD, director of the Scripps Research Translational Institute in La Jolla, Calif., and editor-in-chief of Medscape Medical News.

Pfizer and BioNTech announced the updated findings in a Nov. 4 press release.

A booster dose of the BA.4/BA.5-adapted bivalent vaccine is authorized for emergency use by the Food and Drug Administration for ages 5 years and older. The safety and tolerability profile of the Pfizer/BioNTech bivalent booster remains favorable and similar to the original COVID-19 vaccine, the company reported.

Until recently, the BA.5 Omicron variant was the dominant strain in the United States, but is now getting elbowed out by the subvariants BQ.1.1, BQ.1, and BA.4.6, which together make up almost 45% of the circulating virus.
 

Some skepticism

“It is important to note that these data are press-release level, which does not allow a view of the data totality,” Hana El Sahly, MD, professor of molecular virology and microbiology, Baylor College of Medicine, Houston, said in an interview.

“For example, there may be significant differences between the groups, and the release mentions at least one difference that is of importance: the interval since the last vaccination which often affects the response to subsequent boosting,” she said.

Dr. El Sahly added that the findings are not surprising. “In the short term, a variant-specific vaccine produces a higher level of antibody against the variant in the vaccine than the vaccines based on the ancestral strains.”

More researcher results are warranted. “These data do not indicate that these differences between the two vaccines translate into a meaningful clinical benefit at a population level,” Dr. El Sahly said.
 

An uncertain winter ahead

“As we head into the holiday season, we hope these updated data will encourage people to seek out a COVID-19 bivalent booster as soon as they are eligible in order to maintain high levels of protection against the widely circulating Omicron BA.4 and BA.5 sublineages,” Albert Bourla, Pfizer chairman and CEO, stated in the release.

The updated data from the Pfizer/BioNTech study are “all the more reason to get a booster, with added protection also versus BQ.1.1, which will soon become dominant in the U.S.,” Dr. Topol predicted.

It is unclear when the next surge will happen, as COVID-19 does not always follow a seasonal pattern, at least not yet, Dr. El Sahly said. “Regardless, it is reasonable to recommend additional vaccine doses to immunocompromised and frail or older persons. More importantly, influenza vaccination and being up to date on pneumococcal vaccines are highly recommended as soon as feasible, given the early and intense flu season.”

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has expanded the indication for tenofovir alafenamide (Vemlidy) to children aged 12 years and older with chronic hepatitis B virus (HBV) infection with compensated liver disease, the drug’s manufacturer has announced.

The approval in the pediatric patient population was supported by 24-week data from a phase 2 clinical trial comparing treatment with tenofovir alafenamide (25 mg once daily) with placebo in 70 treatment-naive and treatment-experienced patients aged 12-18 years weighing at least 35 kg.

The study met its primary endpoint of percentage of patients with HBV DNA levels less than 20 IU/mL at 24 weeks of therapy, Gilead Sciences said in a press release.

Overall, 10 of 47 (21%) patients treated with tenofovir alafenamide achieved HBV DNA less than 20 IU/mL at 24 weeks, compared with 0 of 23 (0%) treated with placebo.

The rates of serum ALT normalization were higher with tenofovir alafenamide than with placebo (44% vs 0%).

The mean percent changes in bone mineral density (BMD) from baseline to 24 weeks were numerically similar for tenofovir alafenamide– and placebo-treated patients (2.4% and 1.9% for lumbar spine, and 1.5% and 1.9% for whole body, respectively).

The mean changes from baseline BMD z scores were –0.03 and –0.09 for lumbar spine, and –0.05 and –0.01 for whole body, for tenofovir alafenamide and placebo groups, respectively.

The FDA initially approved the nucleoside analog reverse transcriptase inhibitor in 2016 for adults with chronic HBV.

The drug was approved in Europe in 2017 for chronic HBV infection in adults and adolescents aged 12 years and older weighing at least 35 kg.

Tenofovir alafenamide carries a boxed warning citing risks for lactic acidosis/severe hepatomegaly with steatosis and posttreatment severe acute exacerbation of HBV.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has expanded the indication for tenofovir alafenamide (Vemlidy) to children aged 12 years and older with chronic hepatitis B virus (HBV) infection with compensated liver disease, the drug’s manufacturer has announced.

The approval in the pediatric patient population was supported by 24-week data from a phase 2 clinical trial comparing treatment with tenofovir alafenamide (25 mg once daily) with placebo in 70 treatment-naive and treatment-experienced patients aged 12-18 years weighing at least 35 kg.

The study met its primary endpoint of percentage of patients with HBV DNA levels less than 20 IU/mL at 24 weeks of therapy, Gilead Sciences said in a press release.

Overall, 10 of 47 (21%) patients treated with tenofovir alafenamide achieved HBV DNA less than 20 IU/mL at 24 weeks, compared with 0 of 23 (0%) treated with placebo.

The rates of serum ALT normalization were higher with tenofovir alafenamide than with placebo (44% vs 0%).

The mean percent changes in bone mineral density (BMD) from baseline to 24 weeks were numerically similar for tenofovir alafenamide– and placebo-treated patients (2.4% and 1.9% for lumbar spine, and 1.5% and 1.9% for whole body, respectively).

The mean changes from baseline BMD z scores were –0.03 and –0.09 for lumbar spine, and –0.05 and –0.01 for whole body, for tenofovir alafenamide and placebo groups, respectively.

The FDA initially approved the nucleoside analog reverse transcriptase inhibitor in 2016 for adults with chronic HBV.

The drug was approved in Europe in 2017 for chronic HBV infection in adults and adolescents aged 12 years and older weighing at least 35 kg.

Tenofovir alafenamide carries a boxed warning citing risks for lactic acidosis/severe hepatomegaly with steatosis and posttreatment severe acute exacerbation of HBV.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has expanded the indication for tenofovir alafenamide (Vemlidy) to children aged 12 years and older with chronic hepatitis B virus (HBV) infection with compensated liver disease, the drug’s manufacturer has announced.

The approval in the pediatric patient population was supported by 24-week data from a phase 2 clinical trial comparing treatment with tenofovir alafenamide (25 mg once daily) with placebo in 70 treatment-naive and treatment-experienced patients aged 12-18 years weighing at least 35 kg.

The study met its primary endpoint of percentage of patients with HBV DNA levels less than 20 IU/mL at 24 weeks of therapy, Gilead Sciences said in a press release.

Overall, 10 of 47 (21%) patients treated with tenofovir alafenamide achieved HBV DNA less than 20 IU/mL at 24 weeks, compared with 0 of 23 (0%) treated with placebo.

The rates of serum ALT normalization were higher with tenofovir alafenamide than with placebo (44% vs 0%).

The mean percent changes in bone mineral density (BMD) from baseline to 24 weeks were numerically similar for tenofovir alafenamide– and placebo-treated patients (2.4% and 1.9% for lumbar spine, and 1.5% and 1.9% for whole body, respectively).

The mean changes from baseline BMD z scores were –0.03 and –0.09 for lumbar spine, and –0.05 and –0.01 for whole body, for tenofovir alafenamide and placebo groups, respectively.

The FDA initially approved the nucleoside analog reverse transcriptase inhibitor in 2016 for adults with chronic HBV.

The drug was approved in Europe in 2017 for chronic HBV infection in adults and adolescents aged 12 years and older weighing at least 35 kg.

Tenofovir alafenamide carries a boxed warning citing risks for lactic acidosis/severe hepatomegaly with steatosis and posttreatment severe acute exacerbation of HBV.

A version of this article first appeared on Medscape.com.

New trial data from drugmaker Pfizer shows promising results of a vaccine given to mothers during pregnancy that later protects infants in their first months from the worst effects of respiratory syncytial virus, or RSV.

Pfizer will apply for FDA approval by the end of the year, the company said in a statement Nov. 1.

Trial results are so promising that – after talking with government regulators – the company will stop enrolling new people in the study.

Specifically, the company reported that the vaccine prevented severe illness particularly well during the first 90 days of life, with measurable protection against severe illness continuing through 6 months of age. (That period is when infants are the most fragile if they get sick with RSV.)

RSV is a respiratory illness than can affect anyone, usually resulting in no symptoms or those similar to the common cold. But it can be particularly dangerous – and even deadly – for babies and for people over the age of 65. Pfizer and another drug company, GSK, are developing promising vaccines for older adults, the Washington Post reported.

RSV is the leading cause of hospitalization for infants, the Post noted.

The Pfizer study, called MATISSE, enrolled 7,400 pregnant women in 18 countries worldwide. Those who received the vaccine were given it during the late second to third trimester of pregnancy. Women in the study were monitored for safety through the rest of their pregnancy and 6 months after their children were born. Infants were monitored for at least 1 year for safety and effectiveness; more than half of them were monitored for 2 years.

The Pfizer vaccine works by passing maternal antibodies to the infant during pregnancy, the Post reported, noting that other vaccines transmitted via maternal immunization include those for influenza, diphtheria, tetanus, and pertussis.

Annually, RSV has a devastating impact on young children, hospitalizing tens of thousands and causing up to 300 deaths, data show.

For every 100 children who get RSV under 6 months of age, one or two of them may need to be hospitalized, according to the CDC. Those hospitalized infants may need oxygen, intubation, or even mechanical ventilation to help with breathing.

“Most improve with this type of supportive care and are discharged in a few days,” the CDC said.

“I think this is a big step for protecting babies against RSV and improving overall lung health,” vaccine researcher Barney Graham, PhD, told the Post. “Overall, it’s an exciting time for RSV. It’s also a troubling time, because you see how the patterns of infection have been changed by COVID, and we’re having an earlier, bigger season this year than we have for a couple of years – and it’s causing a lot of hospitalization and misery for people.”

As many as four RSV vaccines may have applications submitted to the FDA in 2022, according to CNN. Also in development is an antibody shot given to infants just after they are born, the news outlet reported.

Pfizer’s data, announced Tuesday, has not yet been published or peer-reviewed, but the company said it is seeking peer-reviewed publication.

“We are thrilled by these data, as this is the first-ever investigational vaccine shown to help protect newborns against severe RSV-related respiratory illness immediately at birth,” Annaliesa Anderson, PhD, Pfizer chief scientific officer for vaccine research & development, said in a statement. “We look forward to working with the FDA and other regulatory agencies to bring this vaccine candidate to expectant mothers to help protect their infants against severe RSV during their most vulnerable first six months of life, which has the highest burden of RSV illness in infants.”

A version of this article first appeared on WebMD.com.

New trial data from drugmaker Pfizer shows promising results of a vaccine given to mothers during pregnancy that later protects infants in their first months from the worst effects of respiratory syncytial virus, or RSV.

Pfizer will apply for FDA approval by the end of the year, the company said in a statement Nov. 1.

Trial results are so promising that – after talking with government regulators – the company will stop enrolling new people in the study.

Specifically, the company reported that the vaccine prevented severe illness particularly well during the first 90 days of life, with measurable protection against severe illness continuing through 6 months of age. (That period is when infants are the most fragile if they get sick with RSV.)

RSV is a respiratory illness than can affect anyone, usually resulting in no symptoms or those similar to the common cold. But it can be particularly dangerous – and even deadly – for babies and for people over the age of 65. Pfizer and another drug company, GSK, are developing promising vaccines for older adults, the Washington Post reported.

RSV is the leading cause of hospitalization for infants, the Post noted.

The Pfizer study, called MATISSE, enrolled 7,400 pregnant women in 18 countries worldwide. Those who received the vaccine were given it during the late second to third trimester of pregnancy. Women in the study were monitored for safety through the rest of their pregnancy and 6 months after their children were born. Infants were monitored for at least 1 year for safety and effectiveness; more than half of them were monitored for 2 years.

The Pfizer vaccine works by passing maternal antibodies to the infant during pregnancy, the Post reported, noting that other vaccines transmitted via maternal immunization include those for influenza, diphtheria, tetanus, and pertussis.

Annually, RSV has a devastating impact on young children, hospitalizing tens of thousands and causing up to 300 deaths, data show.

For every 100 children who get RSV under 6 months of age, one or two of them may need to be hospitalized, according to the CDC. Those hospitalized infants may need oxygen, intubation, or even mechanical ventilation to help with breathing.

“Most improve with this type of supportive care and are discharged in a few days,” the CDC said.

“I think this is a big step for protecting babies against RSV and improving overall lung health,” vaccine researcher Barney Graham, PhD, told the Post. “Overall, it’s an exciting time for RSV. It’s also a troubling time, because you see how the patterns of infection have been changed by COVID, and we’re having an earlier, bigger season this year than we have for a couple of years – and it’s causing a lot of hospitalization and misery for people.”

As many as four RSV vaccines may have applications submitted to the FDA in 2022, according to CNN. Also in development is an antibody shot given to infants just after they are born, the news outlet reported.

Pfizer’s data, announced Tuesday, has not yet been published or peer-reviewed, but the company said it is seeking peer-reviewed publication.

“We are thrilled by these data, as this is the first-ever investigational vaccine shown to help protect newborns against severe RSV-related respiratory illness immediately at birth,” Annaliesa Anderson, PhD, Pfizer chief scientific officer for vaccine research & development, said in a statement. “We look forward to working with the FDA and other regulatory agencies to bring this vaccine candidate to expectant mothers to help protect their infants against severe RSV during their most vulnerable first six months of life, which has the highest burden of RSV illness in infants.”

A version of this article first appeared on WebMD.com.

New trial data from drugmaker Pfizer shows promising results of a vaccine given to mothers during pregnancy that later protects infants in their first months from the worst effects of respiratory syncytial virus, or RSV.

Pfizer will apply for FDA approval by the end of the year, the company said in a statement Nov. 1.

Trial results are so promising that – after talking with government regulators – the company will stop enrolling new people in the study.

Specifically, the company reported that the vaccine prevented severe illness particularly well during the first 90 days of life, with measurable protection against severe illness continuing through 6 months of age. (That period is when infants are the most fragile if they get sick with RSV.)

RSV is a respiratory illness than can affect anyone, usually resulting in no symptoms or those similar to the common cold. But it can be particularly dangerous – and even deadly – for babies and for people over the age of 65. Pfizer and another drug company, GSK, are developing promising vaccines for older adults, the Washington Post reported.

RSV is the leading cause of hospitalization for infants, the Post noted.

The Pfizer study, called MATISSE, enrolled 7,400 pregnant women in 18 countries worldwide. Those who received the vaccine were given it during the late second to third trimester of pregnancy. Women in the study were monitored for safety through the rest of their pregnancy and 6 months after their children were born. Infants were monitored for at least 1 year for safety and effectiveness; more than half of them were monitored for 2 years.

The Pfizer vaccine works by passing maternal antibodies to the infant during pregnancy, the Post reported, noting that other vaccines transmitted via maternal immunization include those for influenza, diphtheria, tetanus, and pertussis.

Annually, RSV has a devastating impact on young children, hospitalizing tens of thousands and causing up to 300 deaths, data show.

For every 100 children who get RSV under 6 months of age, one or two of them may need to be hospitalized, according to the CDC. Those hospitalized infants may need oxygen, intubation, or even mechanical ventilation to help with breathing.

“Most improve with this type of supportive care and are discharged in a few days,” the CDC said.

“I think this is a big step for protecting babies against RSV and improving overall lung health,” vaccine researcher Barney Graham, PhD, told the Post. “Overall, it’s an exciting time for RSV. It’s also a troubling time, because you see how the patterns of infection have been changed by COVID, and we’re having an earlier, bigger season this year than we have for a couple of years – and it’s causing a lot of hospitalization and misery for people.”

As many as four RSV vaccines may have applications submitted to the FDA in 2022, according to CNN. Also in development is an antibody shot given to infants just after they are born, the news outlet reported.

Pfizer’s data, announced Tuesday, has not yet been published or peer-reviewed, but the company said it is seeking peer-reviewed publication.

“We are thrilled by these data, as this is the first-ever investigational vaccine shown to help protect newborns against severe RSV-related respiratory illness immediately at birth,” Annaliesa Anderson, PhD, Pfizer chief scientific officer for vaccine research & development, said in a statement. “We look forward to working with the FDA and other regulatory agencies to bring this vaccine candidate to expectant mothers to help protect their infants against severe RSV during their most vulnerable first six months of life, which has the highest burden of RSV illness in infants.”

A version of this article first appeared on WebMD.com.

The liquid form of the antibiotic amoxicillin often used to treat ear infections and strep throat in children is in short supply, just as Americans head into the season when they use the bacteria-fighting drug the most.

The FDA officially listed the shortage Oct. 28, but pharmacists, hospitals, and a supply tracking database sounded alarms earlier this month.

“The scary part is, we’re coming into the time of the year where you have the greatest need,” independent pharmacy owner Hugh Chancy, PharmD, of Georgia, told NBC News. 

Thus far, reports indicate the impact of the shortages is not widespread but does affect some pharmacies, and at least one hospital has published an algorithm for offering treatment alternatives. 

CVS told Bloomberg News that some stores are experiencing shortages of certain doses of amoxicillin, but a Walmart spokesperson said its diverse supply chain meant none of its pharmacies were affected.

“Hypothetically, if amoxicillin doesn’t come into stock for some time, then we’re potentially having to use less effective antibiotics with more side effects,” said Ohio pediatrician Sean Gallagher, MD, according to Bloomberg.

The shortage impacts three of the four largest amoxicillin manufacturers worldwide, according to the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota. The FDA listed the reason for the shortage as “demand increase for drug,” except in the case of manufacturer Sandoz, for which the reason listed read “information pending.”

A company spokesperson told Bloomberg the reasons were complex.

“The combination in rapid succession of the pandemic impact and consequent demand swings, manufacturing capacity constraints, scarcity of raw materials, and the current energy crisis means we face a uniquely difficult situation in the short term,” Sandoz spokesperson Leslie Pott told Bloomberg.

According to Bloomberg, other major manufacturers are still delivering the product, but limiting new orders.

The American Society of Health-System Pharmacists issued an alert for the shortage last week via its real time drug shortage database.

“Amoxicillin comes in many forms – including capsules, powders and chewable tablets – but the most common type children take is the liquid form, which makes up at least 19 products that are part of the” shortage, Becker’s Hospital Review summarized of the database reports.

The pediatric health system Children’s Minnesota told CIDRAP that supplies are low and that alternatives are being prescribed “when appropriate.”

“As a final step, we temporarily discontinued our standard procedure of dispensing the entire bottle of amoxicillin (which comes in multiple sizes),” a spokesperson told CIDRAP. “We are instead mixing and pouring the exact amount for each course of therapy, to eliminate waste.” 

The Minnesota pediatric clinic and others are particularly on alert because of the surge nationwide of a respiratory virus that particularly impacts children known as RSV.

“We have certainly observed an increase in recent use most likely correlating with the surge in RSV and other respiratory viruses with concern for superimposed bacterial infection in our critically ill and hospitalized patient population,” Laura Bio, PharmD, a clinical pharmacy specialist at Stanford Medicine Children’s Health told CIDRAP.

A version of this article first appeared on WebMD.com.

The liquid form of the antibiotic amoxicillin often used to treat ear infections and strep throat in children is in short supply, just as Americans head into the season when they use the bacteria-fighting drug the most.

The FDA officially listed the shortage Oct. 28, but pharmacists, hospitals, and a supply tracking database sounded alarms earlier this month.

“The scary part is, we’re coming into the time of the year where you have the greatest need,” independent pharmacy owner Hugh Chancy, PharmD, of Georgia, told NBC News. 

Thus far, reports indicate the impact of the shortages is not widespread but does affect some pharmacies, and at least one hospital has published an algorithm for offering treatment alternatives. 

CVS told Bloomberg News that some stores are experiencing shortages of certain doses of amoxicillin, but a Walmart spokesperson said its diverse supply chain meant none of its pharmacies were affected.

“Hypothetically, if amoxicillin doesn’t come into stock for some time, then we’re potentially having to use less effective antibiotics with more side effects,” said Ohio pediatrician Sean Gallagher, MD, according to Bloomberg.

The shortage impacts three of the four largest amoxicillin manufacturers worldwide, according to the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota. The FDA listed the reason for the shortage as “demand increase for drug,” except in the case of manufacturer Sandoz, for which the reason listed read “information pending.”

A company spokesperson told Bloomberg the reasons were complex.

“The combination in rapid succession of the pandemic impact and consequent demand swings, manufacturing capacity constraints, scarcity of raw materials, and the current energy crisis means we face a uniquely difficult situation in the short term,” Sandoz spokesperson Leslie Pott told Bloomberg.

According to Bloomberg, other major manufacturers are still delivering the product, but limiting new orders.

The American Society of Health-System Pharmacists issued an alert for the shortage last week via its real time drug shortage database.

“Amoxicillin comes in many forms – including capsules, powders and chewable tablets – but the most common type children take is the liquid form, which makes up at least 19 products that are part of the” shortage, Becker’s Hospital Review summarized of the database reports.

The pediatric health system Children’s Minnesota told CIDRAP that supplies are low and that alternatives are being prescribed “when appropriate.”

“As a final step, we temporarily discontinued our standard procedure of dispensing the entire bottle of amoxicillin (which comes in multiple sizes),” a spokesperson told CIDRAP. “We are instead mixing and pouring the exact amount for each course of therapy, to eliminate waste.” 

The Minnesota pediatric clinic and others are particularly on alert because of the surge nationwide of a respiratory virus that particularly impacts children known as RSV.

“We have certainly observed an increase in recent use most likely correlating with the surge in RSV and other respiratory viruses with concern for superimposed bacterial infection in our critically ill and hospitalized patient population,” Laura Bio, PharmD, a clinical pharmacy specialist at Stanford Medicine Children’s Health told CIDRAP.

A version of this article first appeared on WebMD.com.

The liquid form of the antibiotic amoxicillin often used to treat ear infections and strep throat in children is in short supply, just as Americans head into the season when they use the bacteria-fighting drug the most.

The FDA officially listed the shortage Oct. 28, but pharmacists, hospitals, and a supply tracking database sounded alarms earlier this month.

“The scary part is, we’re coming into the time of the year where you have the greatest need,” independent pharmacy owner Hugh Chancy, PharmD, of Georgia, told NBC News. 

Thus far, reports indicate the impact of the shortages is not widespread but does affect some pharmacies, and at least one hospital has published an algorithm for offering treatment alternatives. 

CVS told Bloomberg News that some stores are experiencing shortages of certain doses of amoxicillin, but a Walmart spokesperson said its diverse supply chain meant none of its pharmacies were affected.

“Hypothetically, if amoxicillin doesn’t come into stock for some time, then we’re potentially having to use less effective antibiotics with more side effects,” said Ohio pediatrician Sean Gallagher, MD, according to Bloomberg.

The shortage impacts three of the four largest amoxicillin manufacturers worldwide, according to the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota. The FDA listed the reason for the shortage as “demand increase for drug,” except in the case of manufacturer Sandoz, for which the reason listed read “information pending.”

A company spokesperson told Bloomberg the reasons were complex.

“The combination in rapid succession of the pandemic impact and consequent demand swings, manufacturing capacity constraints, scarcity of raw materials, and the current energy crisis means we face a uniquely difficult situation in the short term,” Sandoz spokesperson Leslie Pott told Bloomberg.

According to Bloomberg, other major manufacturers are still delivering the product, but limiting new orders.

The American Society of Health-System Pharmacists issued an alert for the shortage last week via its real time drug shortage database.

“Amoxicillin comes in many forms – including capsules, powders and chewable tablets – but the most common type children take is the liquid form, which makes up at least 19 products that are part of the” shortage, Becker’s Hospital Review summarized of the database reports.

The pediatric health system Children’s Minnesota told CIDRAP that supplies are low and that alternatives are being prescribed “when appropriate.”

“As a final step, we temporarily discontinued our standard procedure of dispensing the entire bottle of amoxicillin (which comes in multiple sizes),” a spokesperson told CIDRAP. “We are instead mixing and pouring the exact amount for each course of therapy, to eliminate waste.” 

The Minnesota pediatric clinic and others are particularly on alert because of the surge nationwide of a respiratory virus that particularly impacts children known as RSV.

“We have certainly observed an increase in recent use most likely correlating with the surge in RSV and other respiratory viruses with concern for superimposed bacterial infection in our critically ill and hospitalized patient population,” Laura Bio, PharmD, a clinical pharmacy specialist at Stanford Medicine Children’s Health told CIDRAP.

A version of this article first appeared on WebMD.com.

Just 3 weeks into the 2022-2023 flu season, the latest data from the Centers for Disease Control and Prevention’s Influenza Division suggest that the flu and respiratory syncytial virus are more than making up for the recent decline in COVID activity.

Outpatient visits for influenzalike illness (ILI), which includes influenza, SARS-CoV-2, and RSV, were higher after 3 weeks than for any of the previous five flu seasons: 3.3% of visits reported through the CDC’s Outpatient Influenza-like Illness Surveillance Network involved ILI as of Oct. 22. The highest comparable rate in the previous 5 years was the 1.9% recorded in late October of 2021, shortly after the definition of ILI was changed to also include illnesses other than influenza.

This season’s higher flu activity is in contrast to the previous two, which were unusually mild. The change, however, is not unexpected, as William Schaffner, MD, an infectious disease expert and professor of preventive medicine at Vanderbilt University, recently told CNN.

“Here we are in the middle of October – not the middle of November – we’re already seeing scattered influenza cases, even hospitalized influenza cases, around the country,” he said. “So we know that this virus is now spreading out in the community already. It’s gathering speed already. It looks to me to be about a month early.”

One indication of the mildness of the previous two flu seasons was the number of deaths, both pediatric and overall. Influenza-associated pediatric deaths had averaged about 110 per season over the previous eight seasons, compared with just 1 for 2020-2021 and 43 in 2021-2022. Overall flu deaths never reached 1% of all weekly deaths for either season, well below baseline levels for the flu, which range from 5.5% to 6.8%, CDC data show.
 

Other indicators of early severity

This season’s early rise in viral activity also can be seen in hospitalizations. The cumulative rate of flu-related admissions was 1.5 per 100,000 population as of Oct. 22, higher than the rate observed in the comparable week of previous seasons going back to 2010-2011, according to the CDC’s Influenza Hospitalization Surveillance Network.

A look at state reports of ILI outpatient visit rates shows that the District of Columbia and South Carolina are already in the very high range of the CDC’s severity scale, while 11 states are in the high range. Again going back to 2010-2011, no jurisdiction has ever been in the very high range this early in the season, based on data from the Outpatient Influenza-like Illness Surveillance Network.

Just 3 weeks into the 2022-2023 flu season, the latest data from the Centers for Disease Control and Prevention’s Influenza Division suggest that the flu and respiratory syncytial virus are more than making up for the recent decline in COVID activity.

Outpatient visits for influenzalike illness (ILI), which includes influenza, SARS-CoV-2, and RSV, were higher after 3 weeks than for any of the previous five flu seasons: 3.3% of visits reported through the CDC’s Outpatient Influenza-like Illness Surveillance Network involved ILI as of Oct. 22. The highest comparable rate in the previous 5 years was the 1.9% recorded in late October of 2021, shortly after the definition of ILI was changed to also include illnesses other than influenza.

This season’s higher flu activity is in contrast to the previous two, which were unusually mild. The change, however, is not unexpected, as William Schaffner, MD, an infectious disease expert and professor of preventive medicine at Vanderbilt University, recently told CNN.

“Here we are in the middle of October – not the middle of November – we’re already seeing scattered influenza cases, even hospitalized influenza cases, around the country,” he said. “So we know that this virus is now spreading out in the community already. It’s gathering speed already. It looks to me to be about a month early.”

One indication of the mildness of the previous two flu seasons was the number of deaths, both pediatric and overall. Influenza-associated pediatric deaths had averaged about 110 per season over the previous eight seasons, compared with just 1 for 2020-2021 and 43 in 2021-2022. Overall flu deaths never reached 1% of all weekly deaths for either season, well below baseline levels for the flu, which range from 5.5% to 6.8%, CDC data show.
 

Other indicators of early severity

This season’s early rise in viral activity also can be seen in hospitalizations. The cumulative rate of flu-related admissions was 1.5 per 100,000 population as of Oct. 22, higher than the rate observed in the comparable week of previous seasons going back to 2010-2011, according to the CDC’s Influenza Hospitalization Surveillance Network.

A look at state reports of ILI outpatient visit rates shows that the District of Columbia and South Carolina are already in the very high range of the CDC’s severity scale, while 11 states are in the high range. Again going back to 2010-2011, no jurisdiction has ever been in the very high range this early in the season, based on data from the Outpatient Influenza-like Illness Surveillance Network.

Just 3 weeks into the 2022-2023 flu season, the latest data from the Centers for Disease Control and Prevention’s Influenza Division suggest that the flu and respiratory syncytial virus are more than making up for the recent decline in COVID activity.

Outpatient visits for influenzalike illness (ILI), which includes influenza, SARS-CoV-2, and RSV, were higher after 3 weeks than for any of the previous five flu seasons: 3.3% of visits reported through the CDC’s Outpatient Influenza-like Illness Surveillance Network involved ILI as of Oct. 22. The highest comparable rate in the previous 5 years was the 1.9% recorded in late October of 2021, shortly after the definition of ILI was changed to also include illnesses other than influenza.

This season’s higher flu activity is in contrast to the previous two, which were unusually mild. The change, however, is not unexpected, as William Schaffner, MD, an infectious disease expert and professor of preventive medicine at Vanderbilt University, recently told CNN.

“Here we are in the middle of October – not the middle of November – we’re already seeing scattered influenza cases, even hospitalized influenza cases, around the country,” he said. “So we know that this virus is now spreading out in the community already. It’s gathering speed already. It looks to me to be about a month early.”

One indication of the mildness of the previous two flu seasons was the number of deaths, both pediatric and overall. Influenza-associated pediatric deaths had averaged about 110 per season over the previous eight seasons, compared with just 1 for 2020-2021 and 43 in 2021-2022. Overall flu deaths never reached 1% of all weekly deaths for either season, well below baseline levels for the flu, which range from 5.5% to 6.8%, CDC data show.
 

Other indicators of early severity

This season’s early rise in viral activity also can be seen in hospitalizations. The cumulative rate of flu-related admissions was 1.5 per 100,000 population as of Oct. 22, higher than the rate observed in the comparable week of previous seasons going back to 2010-2011, according to the CDC’s Influenza Hospitalization Surveillance Network.

A look at state reports of ILI outpatient visit rates shows that the District of Columbia and South Carolina are already in the very high range of the CDC’s severity scale, while 11 states are in the high range. Again going back to 2010-2011, no jurisdiction has ever been in the very high range this early in the season, based on data from the Outpatient Influenza-like Illness Surveillance Network.

The SARS-CoV-2 infection disrupts the normal mix of gut bacteria, allowing harmful bacteria to enter the bloodstream and raising the risk for potentially life-threatening secondary bloodstream infections (BSIs), new research suggests.

“Collectively, these results reveal an unappreciated link between SARS-CoV-2 infection, gut microbiome dysbiosis, and a severe complication of COVID-19, BSIs,” the study team reported in Nature Communications.

“Our findings suggest that coronavirus infection directly interferes with the healthy balance of microbes in the gut, further endangering patients in the process,” microbiologist and co–senior author Ken Cadwell, PhD, New York University, added in a news release. “Now that we have uncovered the source of this bacterial imbalance, physicians can better identify those coronavirus patients most at risk of a secondary bloodstream infection.”

In a mouse model, the researchers first demonstrated that the SARS-CoV-2 infection alone induces gut microbiome dysbiosis and gut epithelial cell alterations, which correlate with markers of gut barrier permeability.

Next, they analyzed the bacterial composition of stool samples from 96 adults hospitalized with COVID-19 in 2020 in New York and New Haven, Conn.

In line with their observations in mice, they found that the SARS-CoV-2 infection is associated with “severe microbiome injury,” characterized by the loss of gut microbiome diversity.

They also observed an increase in populations of several microbes known to include antibiotic-resistant species. An analysis of stool samples paired with blood cultures found that antibiotic-resistant bacteria in the gut migrated to the bloodstream in 20% of patients.

This migration could be caused by a combination of the immune-compromising effects of the viral infection and the antibiotic-driven depletion of commensal gut microbes, the researchers said.

However, COVID-19 patients are also uniquely exposed to other potential factors predisposing them to bacteremia, including immunosuppressive drugs, long hospital stays, and catheters, the investigators noted. The study is limited in its ability to investigate the individual effects of these factors.

“Our findings support a scenario in which gut-to-blood translocation of microorganisms following microbiome dysbiosis leads to dangerous BSIs during COVID-19, a complication seen in other immunocompromised patients, including patients with cancer, acute respiratory distress syndrome, and in ICU patients receiving probiotics,” the researchers wrote.

Investigating the underlying mechanism behind their observations could help inform “the judicious application of antibiotics and immunosuppressives in patients with respiratory viral infections and increase our resilience to pandemics,” they added.

Funding for the study was provided by the National Institutes of Health, the Yale School of Public Health, and numerous other sources. Dr. Cadwell has received research support from Pfizer, Takeda, Pacific Biosciences, Genentech, and AbbVie; consulted for or received an honoraria from PureTech Health, Genentech, and AbbVie; and is named as an inventor on US patent 10,722,600 and provisional patents 62/935,035 and 63/157,225.

A version of this article first appeared on Medscape.com.

The SARS-CoV-2 infection disrupts the normal mix of gut bacteria, allowing harmful bacteria to enter the bloodstream and raising the risk for potentially life-threatening secondary bloodstream infections (BSIs), new research suggests.

“Collectively, these results reveal an unappreciated link between SARS-CoV-2 infection, gut microbiome dysbiosis, and a severe complication of COVID-19, BSIs,” the study team reported in Nature Communications.

“Our findings suggest that coronavirus infection directly interferes with the healthy balance of microbes in the gut, further endangering patients in the process,” microbiologist and co–senior author Ken Cadwell, PhD, New York University, added in a news release. “Now that we have uncovered the source of this bacterial imbalance, physicians can better identify those coronavirus patients most at risk of a secondary bloodstream infection.”

In a mouse model, the researchers first demonstrated that the SARS-CoV-2 infection alone induces gut microbiome dysbiosis and gut epithelial cell alterations, which correlate with markers of gut barrier permeability.

Next, they analyzed the bacterial composition of stool samples from 96 adults hospitalized with COVID-19 in 2020 in New York and New Haven, Conn.

In line with their observations in mice, they found that the SARS-CoV-2 infection is associated with “severe microbiome injury,” characterized by the loss of gut microbiome diversity.

They also observed an increase in populations of several microbes known to include antibiotic-resistant species. An analysis of stool samples paired with blood cultures found that antibiotic-resistant bacteria in the gut migrated to the bloodstream in 20% of patients.

This migration could be caused by a combination of the immune-compromising effects of the viral infection and the antibiotic-driven depletion of commensal gut microbes, the researchers said.

However, COVID-19 patients are also uniquely exposed to other potential factors predisposing them to bacteremia, including immunosuppressive drugs, long hospital stays, and catheters, the investigators noted. The study is limited in its ability to investigate the individual effects of these factors.

“Our findings support a scenario in which gut-to-blood translocation of microorganisms following microbiome dysbiosis leads to dangerous BSIs during COVID-19, a complication seen in other immunocompromised patients, including patients with cancer, acute respiratory distress syndrome, and in ICU patients receiving probiotics,” the researchers wrote.

Investigating the underlying mechanism behind their observations could help inform “the judicious application of antibiotics and immunosuppressives in patients with respiratory viral infections and increase our resilience to pandemics,” they added.

Funding for the study was provided by the National Institutes of Health, the Yale School of Public Health, and numerous other sources. Dr. Cadwell has received research support from Pfizer, Takeda, Pacific Biosciences, Genentech, and AbbVie; consulted for or received an honoraria from PureTech Health, Genentech, and AbbVie; and is named as an inventor on US patent 10,722,600 and provisional patents 62/935,035 and 63/157,225.

A version of this article first appeared on Medscape.com.

The SARS-CoV-2 infection disrupts the normal mix of gut bacteria, allowing harmful bacteria to enter the bloodstream and raising the risk for potentially life-threatening secondary bloodstream infections (BSIs), new research suggests.

“Collectively, these results reveal an unappreciated link between SARS-CoV-2 infection, gut microbiome dysbiosis, and a severe complication of COVID-19, BSIs,” the study team reported in Nature Communications.

“Our findings suggest that coronavirus infection directly interferes with the healthy balance of microbes in the gut, further endangering patients in the process,” microbiologist and co–senior author Ken Cadwell, PhD, New York University, added in a news release. “Now that we have uncovered the source of this bacterial imbalance, physicians can better identify those coronavirus patients most at risk of a secondary bloodstream infection.”

In a mouse model, the researchers first demonstrated that the SARS-CoV-2 infection alone induces gut microbiome dysbiosis and gut epithelial cell alterations, which correlate with markers of gut barrier permeability.

Next, they analyzed the bacterial composition of stool samples from 96 adults hospitalized with COVID-19 in 2020 in New York and New Haven, Conn.

In line with their observations in mice, they found that the SARS-CoV-2 infection is associated with “severe microbiome injury,” characterized by the loss of gut microbiome diversity.

They also observed an increase in populations of several microbes known to include antibiotic-resistant species. An analysis of stool samples paired with blood cultures found that antibiotic-resistant bacteria in the gut migrated to the bloodstream in 20% of patients.

This migration could be caused by a combination of the immune-compromising effects of the viral infection and the antibiotic-driven depletion of commensal gut microbes, the researchers said.

However, COVID-19 patients are also uniquely exposed to other potential factors predisposing them to bacteremia, including immunosuppressive drugs, long hospital stays, and catheters, the investigators noted. The study is limited in its ability to investigate the individual effects of these factors.

“Our findings support a scenario in which gut-to-blood translocation of microorganisms following microbiome dysbiosis leads to dangerous BSIs during COVID-19, a complication seen in other immunocompromised patients, including patients with cancer, acute respiratory distress syndrome, and in ICU patients receiving probiotics,” the researchers wrote.

Investigating the underlying mechanism behind their observations could help inform “the judicious application of antibiotics and immunosuppressives in patients with respiratory viral infections and increase our resilience to pandemics,” they added.

Funding for the study was provided by the National Institutes of Health, the Yale School of Public Health, and numerous other sources. Dr. Cadwell has received research support from Pfizer, Takeda, Pacific Biosciences, Genentech, and AbbVie; consulted for or received an honoraria from PureTech Health, Genentech, and AbbVie; and is named as an inventor on US patent 10,722,600 and provisional patents 62/935,035 and 63/157,225.

A version of this article first appeared on Medscape.com.

Mycetoma is a chronic subcutaneous infection due to fungal (eumycetoma) or aerobic actinomycetes (actinomycetoma) organisms. Clinical lesions develop from a granulomatous infiltrate organizing around the infectious organism. Patients can present with extensive subcutaneous nodularity and draining sinuses that can lead to deformation of the affected extremity. These infections are rare in developed countries, and the prevalence and incidence remain unknown. It has been reported that actinomycetes represent 60% of mycetoma cases worldwide, with the majority of cases in Central America from Nocardia (86%) and Actinomadura madurae (10%). ¹Gordonia species are aerobic, partially acid-fast, gram-positive actinobacteria that may comprise a notable minority of actinomycete isolates. ² The species Gordonia bronchialis is of particular interest as a human pathogen because of increasing reports of nosocomial infections. ^3,4 We describe a case of a mycetomalike infection due to G bronchialis in an immunocompetent patient with complete resolution after 3 months of antibiotics.

Case Report

An 86-year-old man presented to the emergency department with a pruritic rash on the right forearm. He had a history of chronic kidney disease, hypertension, and inverse psoriasis complicated by steroid atrophy. He reported trauma to the right antecubital fossa approximately 1 to 2 months prior from a car door; he received wound care over several weeks at an outside hospital. The initial wound healed completely, but he subsequently noticed erythema spreading down the forearm. At the current presentation, he was empirically treated with mid-potency topical steroids and cefuroxime for 7 days. Initial laboratory results were notable for a white blood cell count of 5.7×10³ cells/μL (reference range,3.7–8.4×10³ cells/μL) and a creatinine level of 1.5 mg/dL (reference range, 0.57–1.25 mg/dL). The patient returned to the emergency department 2 weeks later with spreading of the initial rash and worsening pruritus. Dermatologic evaluation revealed the patient was afebrile and had violaceous papules and nodules that coalesced into plaques on the right arm, with the largest measuring approximately 15 cm. Areas of superficial erosion and crusting were noted (Figure 1A). The patient denied constitutional symptoms and had no axillary or cervical lymphadenopathy. The differential initially included an atypical infection vs a neoplasm. Two 5-mm punch biopsies were performed, which demonstrated a suppurative granulomatous infiltrate in the dermis with extension into the subcutis (Figure 2A). Focal vacuolations within the dermis demonstrated aggregates of gram-positive pseudofilamentous organisms (Figures 2B and 2C). Aerobic tissue cultures grew G bronchialis that was susceptible to all antibiotics tested and Staphylococcus epidermidis. Fungal and mycobacterial cultures were negative. The patient was placed on amoxicillin 875 mg–clavulanate 125 mg twice daily for 3 weeks. However, he demonstrated progression of the rash, with increased induration and confluence of plaques on the forearm (Figure 1B). A repeat excisional biopsy was performed, and a tissue sample was sent for 16S ribosomal RNA sequencing identification. However, neither conventional cultures nor sequencing demonstrated evidence of G bronchialis or any other pathogen. Additionally, bacterial, fungal, and mycobacterial blood cultures were negative. Amoxicillin-clavulanate was stopped, and he was placed on trimethoprim-sulfamethoxazole for 2 weeks, then changed to linezolid (600 mg twice daily) due to continued lack of improvement of the rash. After 2 weeks of linezolid, the rash was slightly improved, but the patient had notable side effects (eg, nausea, mucositis). Therefore, he was switched back to trimethoprim-sulfamethoxazole for another 6 weeks. Antibiotic therapy was discontinued after there was notable regression of indurated plaques (Figure 1C); he received more than 3 months of antibiotics in all. At 1 month after completion of antibiotic therapy, the patient had no evidence of recurrence.

Comment

Microbiology of Gordonia Species—Gordonia bronchialis originally was isolated in 1971 by Tsukamura et al⁵ from the sputum of patients with cavitary tuberculosis and bronchiectasis in Japan. Other Gordonia species (formerly Rhodococcus or Gordona) later were identified in soil, seawater, sediment, and wastewater. Gordonia bronchialis is a gram-positive aerobic actinomycete short rod that organizes in cordlike compact groups. It is weakly acid fast, nonmotile, and nonsporulating. Colonies exhibit pinkish-brown pigmentation. Our understanding of the clinical significance of this organism continues to evolve, and it is not always clearly pathogenic. Because Gordonia isolates may be dismissed as commensals or misidentified as Nocardia or Rhodococcus by routine biochemical tests, it is possible that infections may go undetected. Speciation requires gene sequencing; as our utilization of molecular methods has increased, the identification of clinically relevant aerobic actinomycetes, including Gordonia, has improved,⁶ and the following species have been recognized as pathogens: Gordonia araii, G bronchialis, Gordonia effusa, Gordonia otitidis, Gordonia polyisoprenivorans, Gordonia rubirpertincta, Gordonia sputi, and Gordonia terrae.⁷

Cases Reported in the Literature—A PubMed search of articles indexed for MEDLINE using the term Gordonia bronchialis yielded 35 previously reported human cases of G bronchialis infection, most often associated with medical devices or procedures.^8-31 Eighteen of these cases were sternal surgical site infections in patients with a history of cardiac surgery,^3,4,12-16,30 including 2 outbreaks following coronary artery bypass grafting that were thought to be related to intraoperative transmission from a nurse.^3,4 Of the remaining cases, 12 were linked to a procedure or an indwelling catheter: 4 cases of peritonitis in the setting of continuous ambulatory peritoneal dialysis^17,18,26,27; 3 cases of skin and soft tissue infection (1 at the site of a prior needle injection,¹⁰ 1 after acupuncture,¹¹ and 1 after breast reduction surgery²⁹); 1 case of ventriculitis in a premature neonate with an underlying intraventricular shunt¹⁹; 2 cases of pacemaker-induced endocarditis^20,28; 1 case of tibial osteomyelitis related to a bioresorbable polymer screw²¹; and 1 case of chronic endophthalmitis with underlying intraocular lens implants.²² The Table lists all cases of G bronchialis skin or surgical site infections encountered in our literature search as well as the treatment provided in each case.

Only 4 of these 35 cases of G bronchialis infections were skin and soft tissue infections. All 4 occurred in immunocompetent hosts, and 3 were associated with needle punctures or surgery. The fourth case involved a recurrent breast abscess that occurred in a patient without known risk factors or recent procedures.²³ Other Gordonia species have been associated with cutaneous infections, including Gordonia amicalis, G terrae, and recently Gordonia westfalica, with the latter 2 demonstrating actinomycetoma formation.^32-34 Our case is remarkable in that it represents actinomycetoma due to G bronchialis. Of note, our patient was immunocompetent and did not have any radiation or chronic lymphedema involving the affected extremity. However, his history of steroid-induced skin atrophy may have predisposed him to this rare infection.

Clinical Presentation—Classic mycetoma demonstrate organismal granules within the dermis, surrounded by a neutrophilic infiltrate, which is in turn surrounded by histiocytes and multinucleated giant cells. Periodic acid–Schiff and silver stains can identify fungal organisms, while Gram stain helps to elucidate bacterial etiologies.¹ In our patient, a biopsy revealed several dermal aggregates of pseudofilamentous gram-positive organisms surrounded by a neutrophilic and histiocytic infiltrate.⁸ Because this case presented over weeks to months rather than months to years, it progressed more rapidly than a classic mycetoma. However, the dermatologic and histologic features were consistent with mycetoma.

Management—General treatment of actinomycetoma requires identification of the causative organism and prolonged administration of antibiotics, typically in combination.^35-37 Most G bronchialis infections associated with surgical intervention or implants in the literature required surgical debridement and removal of contaminated material for clinical cure, with the exception of 3 cases of sternal wound infection and 1 case of peritonitis that recovered with antimicrobial therapy alone.^3,17 Combination therapy often was used, but monotherapy, particularly with a fluoroquinolone, has been reported. Susceptibility data are limited, but in general, Gordonia species appear susceptible to imipenem, ciprofloxacin, amikacin, gentamicin, and linezolid, with variable susceptibility to vancomycin (89% of isolates), third-generation cephalosporins (80%–90% of isolates), tetracyclines (≤85% of isolates), penicillin (≤70% of isolates), and trimethoprim-sulfamethoxazole (≤65% of isolates).^{7,10,19,38-40} Although there are no standardized recommendations for the treatment of these infections, the most commonly used drugs to treat Gordonia are carbapenems and fluoroquinolones, with or without an aminoglycoside, followed by third-generation cephalosporins and vancomycin, depending on susceptibilities. Additional antibiotics (alone or in combination) that have previously been used with favorable outcomes include amoxicillin or amoxicillin-clavulanate, piperacillin-tazobactam, rifampicin, trimethoprim-sulfamethoxazole, minocycline, doxycycline, and daptomycin.

Our patient received amoxicillin-clavulanate, trimethoprim-sulfamethoxazole, and linezolid. We considered combination therapy but decided against it due to concern for toxicity, given his age and poor renal function. The antibiotic that was most important to his recovery was unclear; the patient insisted that his body, not antibiotics, deserved most of the credit for healing his arm. Although cultures and polymerase chain reaction assays were negative after 3 weeks of amoxicillin-clavulanate, the patient did not show clinical improvement—reasons could be because the antibiotic reduced but did not eliminate the bacterial burden, sampling error of the biopsy, or it takes much longer for the body to heal than it takes to kill the bacteria. Most likely a combination of factors was at play.

Conclusion

Gordonia bronchialis is an emerging cause of human infections typically occurring after trauma, inoculation, or surgery. Most infections are localized; however, the present case highlights the ability of this species to form a massive cutaneous infection. Treatment should be tailored to susceptibility, with close follow-up to ensure improvement and resolution. For clinicians encountering a similar case, we encourage biopsy prior to empiric antibiotics, as antibiotic therapy can decrease the yield of subsequent testing. Treatment should be guided by the clinical course and may need to last weeks to months. Combination therapy for Gordonia infections should be considered in severe cases, in cases presenting as actinomycetoma, in those not responding to therapy, or when the susceptibility profile is unknown or unreliable.

Acknowledgments—The authors thank this veteran for allowing us to participate in his care and to learn from his experience. He gave his consent for us to share his story and the photographs of the arm.

Mycetoma is a chronic subcutaneous infection due to fungal (eumycetoma) or aerobic actinomycetes (actinomycetoma) organisms. Clinical lesions develop from a granulomatous infiltrate organizing around the infectious organism. Patients can present with extensive subcutaneous nodularity and draining sinuses that can lead to deformation of the affected extremity. These infections are rare in developed countries, and the prevalence and incidence remain unknown. It has been reported that actinomycetes represent 60% of mycetoma cases worldwide, with the majority of cases in Central America from Nocardia (86%) and Actinomadura madurae (10%). ¹Gordonia species are aerobic, partially acid-fast, gram-positive actinobacteria that may comprise a notable minority of actinomycete isolates. ² The species Gordonia bronchialis is of particular interest as a human pathogen because of increasing reports of nosocomial infections. ^3,4 We describe a case of a mycetomalike infection due to G bronchialis in an immunocompetent patient with complete resolution after 3 months of antibiotics.

Case Report

An 86-year-old man presented to the emergency department with a pruritic rash on the right forearm. He had a history of chronic kidney disease, hypertension, and inverse psoriasis complicated by steroid atrophy. He reported trauma to the right antecubital fossa approximately 1 to 2 months prior from a car door; he received wound care over several weeks at an outside hospital. The initial wound healed completely, but he subsequently noticed erythema spreading down the forearm. At the current presentation, he was empirically treated with mid-potency topical steroids and cefuroxime for 7 days. Initial laboratory results were notable for a white blood cell count of 5.7×10³ cells/μL (reference range,3.7–8.4×10³ cells/μL) and a creatinine level of 1.5 mg/dL (reference range, 0.57–1.25 mg/dL). The patient returned to the emergency department 2 weeks later with spreading of the initial rash and worsening pruritus. Dermatologic evaluation revealed the patient was afebrile and had violaceous papules and nodules that coalesced into plaques on the right arm, with the largest measuring approximately 15 cm. Areas of superficial erosion and crusting were noted (Figure 1A). The patient denied constitutional symptoms and had no axillary or cervical lymphadenopathy. The differential initially included an atypical infection vs a neoplasm. Two 5-mm punch biopsies were performed, which demonstrated a suppurative granulomatous infiltrate in the dermis with extension into the subcutis (Figure 2A). Focal vacuolations within the dermis demonstrated aggregates of gram-positive pseudofilamentous organisms (Figures 2B and 2C). Aerobic tissue cultures grew G bronchialis that was susceptible to all antibiotics tested and Staphylococcus epidermidis. Fungal and mycobacterial cultures were negative. The patient was placed on amoxicillin 875 mg–clavulanate 125 mg twice daily for 3 weeks. However, he demonstrated progression of the rash, with increased induration and confluence of plaques on the forearm (Figure 1B). A repeat excisional biopsy was performed, and a tissue sample was sent for 16S ribosomal RNA sequencing identification. However, neither conventional cultures nor sequencing demonstrated evidence of G bronchialis or any other pathogen. Additionally, bacterial, fungal, and mycobacterial blood cultures were negative. Amoxicillin-clavulanate was stopped, and he was placed on trimethoprim-sulfamethoxazole for 2 weeks, then changed to linezolid (600 mg twice daily) due to continued lack of improvement of the rash. After 2 weeks of linezolid, the rash was slightly improved, but the patient had notable side effects (eg, nausea, mucositis). Therefore, he was switched back to trimethoprim-sulfamethoxazole for another 6 weeks. Antibiotic therapy was discontinued after there was notable regression of indurated plaques (Figure 1C); he received more than 3 months of antibiotics in all. At 1 month after completion of antibiotic therapy, the patient had no evidence of recurrence.

Comment

Microbiology of Gordonia Species—Gordonia bronchialis originally was isolated in 1971 by Tsukamura et al⁵ from the sputum of patients with cavitary tuberculosis and bronchiectasis in Japan. Other Gordonia species (formerly Rhodococcus or Gordona) later were identified in soil, seawater, sediment, and wastewater. Gordonia bronchialis is a gram-positive aerobic actinomycete short rod that organizes in cordlike compact groups. It is weakly acid fast, nonmotile, and nonsporulating. Colonies exhibit pinkish-brown pigmentation. Our understanding of the clinical significance of this organism continues to evolve, and it is not always clearly pathogenic. Because Gordonia isolates may be dismissed as commensals or misidentified as Nocardia or Rhodococcus by routine biochemical tests, it is possible that infections may go undetected. Speciation requires gene sequencing; as our utilization of molecular methods has increased, the identification of clinically relevant aerobic actinomycetes, including Gordonia, has improved,⁶ and the following species have been recognized as pathogens: Gordonia araii, G bronchialis, Gordonia effusa, Gordonia otitidis, Gordonia polyisoprenivorans, Gordonia rubirpertincta, Gordonia sputi, and Gordonia terrae.⁷

Cases Reported in the Literature—A PubMed search of articles indexed for MEDLINE using the term Gordonia bronchialis yielded 35 previously reported human cases of G bronchialis infection, most often associated with medical devices or procedures.^8-31 Eighteen of these cases were sternal surgical site infections in patients with a history of cardiac surgery,^3,4,12-16,30 including 2 outbreaks following coronary artery bypass grafting that were thought to be related to intraoperative transmission from a nurse.^3,4 Of the remaining cases, 12 were linked to a procedure or an indwelling catheter: 4 cases of peritonitis in the setting of continuous ambulatory peritoneal dialysis^17,18,26,27; 3 cases of skin and soft tissue infection (1 at the site of a prior needle injection,¹⁰ 1 after acupuncture,¹¹ and 1 after breast reduction surgery²⁹); 1 case of ventriculitis in a premature neonate with an underlying intraventricular shunt¹⁹; 2 cases of pacemaker-induced endocarditis^20,28; 1 case of tibial osteomyelitis related to a bioresorbable polymer screw²¹; and 1 case of chronic endophthalmitis with underlying intraocular lens implants.²² The Table lists all cases of G bronchialis skin or surgical site infections encountered in our literature search as well as the treatment provided in each case.

Only 4 of these 35 cases of G bronchialis infections were skin and soft tissue infections. All 4 occurred in immunocompetent hosts, and 3 were associated with needle punctures or surgery. The fourth case involved a recurrent breast abscess that occurred in a patient without known risk factors or recent procedures.²³ Other Gordonia species have been associated with cutaneous infections, including Gordonia amicalis, G terrae, and recently Gordonia westfalica, with the latter 2 demonstrating actinomycetoma formation.^32-34 Our case is remarkable in that it represents actinomycetoma due to G bronchialis. Of note, our patient was immunocompetent and did not have any radiation or chronic lymphedema involving the affected extremity. However, his history of steroid-induced skin atrophy may have predisposed him to this rare infection.

Clinical Presentation—Classic mycetoma demonstrate organismal granules within the dermis, surrounded by a neutrophilic infiltrate, which is in turn surrounded by histiocytes and multinucleated giant cells. Periodic acid–Schiff and silver stains can identify fungal organisms, while Gram stain helps to elucidate bacterial etiologies.¹ In our patient, a biopsy revealed several dermal aggregates of pseudofilamentous gram-positive organisms surrounded by a neutrophilic and histiocytic infiltrate.⁸ Because this case presented over weeks to months rather than months to years, it progressed more rapidly than a classic mycetoma. However, the dermatologic and histologic features were consistent with mycetoma.

Management—General treatment of actinomycetoma requires identification of the causative organism and prolonged administration of antibiotics, typically in combination.^35-37 Most G bronchialis infections associated with surgical intervention or implants in the literature required surgical debridement and removal of contaminated material for clinical cure, with the exception of 3 cases of sternal wound infection and 1 case of peritonitis that recovered with antimicrobial therapy alone.^3,17 Combination therapy often was used, but monotherapy, particularly with a fluoroquinolone, has been reported. Susceptibility data are limited, but in general, Gordonia species appear susceptible to imipenem, ciprofloxacin, amikacin, gentamicin, and linezolid, with variable susceptibility to vancomycin (89% of isolates), third-generation cephalosporins (80%–90% of isolates), tetracyclines (≤85% of isolates), penicillin (≤70% of isolates), and trimethoprim-sulfamethoxazole (≤65% of isolates).^{7,10,19,38-40} Although there are no standardized recommendations for the treatment of these infections, the most commonly used drugs to treat Gordonia are carbapenems and fluoroquinolones, with or without an aminoglycoside, followed by third-generation cephalosporins and vancomycin, depending on susceptibilities. Additional antibiotics (alone or in combination) that have previously been used with favorable outcomes include amoxicillin or amoxicillin-clavulanate, piperacillin-tazobactam, rifampicin, trimethoprim-sulfamethoxazole, minocycline, doxycycline, and daptomycin.

Our patient received amoxicillin-clavulanate, trimethoprim-sulfamethoxazole, and linezolid. We considered combination therapy but decided against it due to concern for toxicity, given his age and poor renal function. The antibiotic that was most important to his recovery was unclear; the patient insisted that his body, not antibiotics, deserved most of the credit for healing his arm. Although cultures and polymerase chain reaction assays were negative after 3 weeks of amoxicillin-clavulanate, the patient did not show clinical improvement—reasons could be because the antibiotic reduced but did not eliminate the bacterial burden, sampling error of the biopsy, or it takes much longer for the body to heal than it takes to kill the bacteria. Most likely a combination of factors was at play.

Conclusion

Gordonia bronchialis is an emerging cause of human infections typically occurring after trauma, inoculation, or surgery. Most infections are localized; however, the present case highlights the ability of this species to form a massive cutaneous infection. Treatment should be tailored to susceptibility, with close follow-up to ensure improvement and resolution. For clinicians encountering a similar case, we encourage biopsy prior to empiric antibiotics, as antibiotic therapy can decrease the yield of subsequent testing. Treatment should be guided by the clinical course and may need to last weeks to months. Combination therapy for Gordonia infections should be considered in severe cases, in cases presenting as actinomycetoma, in those not responding to therapy, or when the susceptibility profile is unknown or unreliable.

Acknowledgments—The authors thank this veteran for allowing us to participate in his care and to learn from his experience. He gave his consent for us to share his story and the photographs of the arm.

Mycetoma is a chronic subcutaneous infection due to fungal (eumycetoma) or aerobic actinomycetes (actinomycetoma) organisms. Clinical lesions develop from a granulomatous infiltrate organizing around the infectious organism. Patients can present with extensive subcutaneous nodularity and draining sinuses that can lead to deformation of the affected extremity. These infections are rare in developed countries, and the prevalence and incidence remain unknown. It has been reported that actinomycetes represent 60% of mycetoma cases worldwide, with the majority of cases in Central America from Nocardia (86%) and Actinomadura madurae (10%). ¹Gordonia species are aerobic, partially acid-fast, gram-positive actinobacteria that may comprise a notable minority of actinomycete isolates. ² The species Gordonia bronchialis is of particular interest as a human pathogen because of increasing reports of nosocomial infections. ^3,4 We describe a case of a mycetomalike infection due to G bronchialis in an immunocompetent patient with complete resolution after 3 months of antibiotics.

Case Report

An 86-year-old man presented to the emergency department with a pruritic rash on the right forearm. He had a history of chronic kidney disease, hypertension, and inverse psoriasis complicated by steroid atrophy. He reported trauma to the right antecubital fossa approximately 1 to 2 months prior from a car door; he received wound care over several weeks at an outside hospital. The initial wound healed completely, but he subsequently noticed erythema spreading down the forearm. At the current presentation, he was empirically treated with mid-potency topical steroids and cefuroxime for 7 days. Initial laboratory results were notable for a white blood cell count of 5.7×10³ cells/μL (reference range,3.7–8.4×10³ cells/μL) and a creatinine level of 1.5 mg/dL (reference range, 0.57–1.25 mg/dL). The patient returned to the emergency department 2 weeks later with spreading of the initial rash and worsening pruritus. Dermatologic evaluation revealed the patient was afebrile and had violaceous papules and nodules that coalesced into plaques on the right arm, with the largest measuring approximately 15 cm. Areas of superficial erosion and crusting were noted (Figure 1A). The patient denied constitutional symptoms and had no axillary or cervical lymphadenopathy. The differential initially included an atypical infection vs a neoplasm. Two 5-mm punch biopsies were performed, which demonstrated a suppurative granulomatous infiltrate in the dermis with extension into the subcutis (Figure 2A). Focal vacuolations within the dermis demonstrated aggregates of gram-positive pseudofilamentous organisms (Figures 2B and 2C). Aerobic tissue cultures grew G bronchialis that was susceptible to all antibiotics tested and Staphylococcus epidermidis. Fungal and mycobacterial cultures were negative. The patient was placed on amoxicillin 875 mg–clavulanate 125 mg twice daily for 3 weeks. However, he demonstrated progression of the rash, with increased induration and confluence of plaques on the forearm (Figure 1B). A repeat excisional biopsy was performed, and a tissue sample was sent for 16S ribosomal RNA sequencing identification. However, neither conventional cultures nor sequencing demonstrated evidence of G bronchialis or any other pathogen. Additionally, bacterial, fungal, and mycobacterial blood cultures were negative. Amoxicillin-clavulanate was stopped, and he was placed on trimethoprim-sulfamethoxazole for 2 weeks, then changed to linezolid (600 mg twice daily) due to continued lack of improvement of the rash. After 2 weeks of linezolid, the rash was slightly improved, but the patient had notable side effects (eg, nausea, mucositis). Therefore, he was switched back to trimethoprim-sulfamethoxazole for another 6 weeks. Antibiotic therapy was discontinued after there was notable regression of indurated plaques (Figure 1C); he received more than 3 months of antibiotics in all. At 1 month after completion of antibiotic therapy, the patient had no evidence of recurrence.

Comment

Microbiology of Gordonia Species—Gordonia bronchialis originally was isolated in 1971 by Tsukamura et al⁵ from the sputum of patients with cavitary tuberculosis and bronchiectasis in Japan. Other Gordonia species (formerly Rhodococcus or Gordona) later were identified in soil, seawater, sediment, and wastewater. Gordonia bronchialis is a gram-positive aerobic actinomycete short rod that organizes in cordlike compact groups. It is weakly acid fast, nonmotile, and nonsporulating. Colonies exhibit pinkish-brown pigmentation. Our understanding of the clinical significance of this organism continues to evolve, and it is not always clearly pathogenic. Because Gordonia isolates may be dismissed as commensals or misidentified as Nocardia or Rhodococcus by routine biochemical tests, it is possible that infections may go undetected. Speciation requires gene sequencing; as our utilization of molecular methods has increased, the identification of clinically relevant aerobic actinomycetes, including Gordonia, has improved,⁶ and the following species have been recognized as pathogens: Gordonia araii, G bronchialis, Gordonia effusa, Gordonia otitidis, Gordonia polyisoprenivorans, Gordonia rubirpertincta, Gordonia sputi, and Gordonia terrae.⁷

Cases Reported in the Literature—A PubMed search of articles indexed for MEDLINE using the term Gordonia bronchialis yielded 35 previously reported human cases of G bronchialis infection, most often associated with medical devices or procedures.^8-31 Eighteen of these cases were sternal surgical site infections in patients with a history of cardiac surgery,^3,4,12-16,30 including 2 outbreaks following coronary artery bypass grafting that were thought to be related to intraoperative transmission from a nurse.^3,4 Of the remaining cases, 12 were linked to a procedure or an indwelling catheter: 4 cases of peritonitis in the setting of continuous ambulatory peritoneal dialysis^17,18,26,27; 3 cases of skin and soft tissue infection (1 at the site of a prior needle injection,¹⁰ 1 after acupuncture,¹¹ and 1 after breast reduction surgery²⁹); 1 case of ventriculitis in a premature neonate with an underlying intraventricular shunt¹⁹; 2 cases of pacemaker-induced endocarditis^20,28; 1 case of tibial osteomyelitis related to a bioresorbable polymer screw²¹; and 1 case of chronic endophthalmitis with underlying intraocular lens implants.²² The Table lists all cases of G bronchialis skin or surgical site infections encountered in our literature search as well as the treatment provided in each case.

Only 4 of these 35 cases of G bronchialis infections were skin and soft tissue infections. All 4 occurred in immunocompetent hosts, and 3 were associated with needle punctures or surgery. The fourth case involved a recurrent breast abscess that occurred in a patient without known risk factors or recent procedures.²³ Other Gordonia species have been associated with cutaneous infections, including Gordonia amicalis, G terrae, and recently Gordonia westfalica, with the latter 2 demonstrating actinomycetoma formation.^32-34 Our case is remarkable in that it represents actinomycetoma due to G bronchialis. Of note, our patient was immunocompetent and did not have any radiation or chronic lymphedema involving the affected extremity. However, his history of steroid-induced skin atrophy may have predisposed him to this rare infection.

Clinical Presentation—Classic mycetoma demonstrate organismal granules within the dermis, surrounded by a neutrophilic infiltrate, which is in turn surrounded by histiocytes and multinucleated giant cells. Periodic acid–Schiff and silver stains can identify fungal organisms, while Gram stain helps to elucidate bacterial etiologies.¹ In our patient, a biopsy revealed several dermal aggregates of pseudofilamentous gram-positive organisms surrounded by a neutrophilic and histiocytic infiltrate.⁸ Because this case presented over weeks to months rather than months to years, it progressed more rapidly than a classic mycetoma. However, the dermatologic and histologic features were consistent with mycetoma.

Management—General treatment of actinomycetoma requires identification of the causative organism and prolonged administration of antibiotics, typically in combination.^35-37 Most G bronchialis infections associated with surgical intervention or implants in the literature required surgical debridement and removal of contaminated material for clinical cure, with the exception of 3 cases of sternal wound infection and 1 case of peritonitis that recovered with antimicrobial therapy alone.^3,17 Combination therapy often was used, but monotherapy, particularly with a fluoroquinolone, has been reported. Susceptibility data are limited, but in general, Gordonia species appear susceptible to imipenem, ciprofloxacin, amikacin, gentamicin, and linezolid, with variable susceptibility to vancomycin (89% of isolates), third-generation cephalosporins (80%–90% of isolates), tetracyclines (≤85% of isolates), penicillin (≤70% of isolates), and trimethoprim-sulfamethoxazole (≤65% of isolates).^{7,10,19,38-40} Although there are no standardized recommendations for the treatment of these infections, the most commonly used drugs to treat Gordonia are carbapenems and fluoroquinolones, with or without an aminoglycoside, followed by third-generation cephalosporins and vancomycin, depending on susceptibilities. Additional antibiotics (alone or in combination) that have previously been used with favorable outcomes include amoxicillin or amoxicillin-clavulanate, piperacillin-tazobactam, rifampicin, trimethoprim-sulfamethoxazole, minocycline, doxycycline, and daptomycin.

Our patient received amoxicillin-clavulanate, trimethoprim-sulfamethoxazole, and linezolid. We considered combination therapy but decided against it due to concern for toxicity, given his age and poor renal function. The antibiotic that was most important to his recovery was unclear; the patient insisted that his body, not antibiotics, deserved most of the credit for healing his arm. Although cultures and polymerase chain reaction assays were negative after 3 weeks of amoxicillin-clavulanate, the patient did not show clinical improvement—reasons could be because the antibiotic reduced but did not eliminate the bacterial burden, sampling error of the biopsy, or it takes much longer for the body to heal than it takes to kill the bacteria. Most likely a combination of factors was at play.

Conclusion

Gordonia bronchialis is an emerging cause of human infections typically occurring after trauma, inoculation, or surgery. Most infections are localized; however, the present case highlights the ability of this species to form a massive cutaneous infection. Treatment should be tailored to susceptibility, with close follow-up to ensure improvement and resolution. For clinicians encountering a similar case, we encourage biopsy prior to empiric antibiotics, as antibiotic therapy can decrease the yield of subsequent testing. Treatment should be guided by the clinical course and may need to last weeks to months. Combination therapy for Gordonia infections should be considered in severe cases, in cases presenting as actinomycetoma, in those not responding to therapy, or when the susceptibility profile is unknown or unreliable.

Acknowledgments—The authors thank this veteran for allowing us to participate in his care and to learn from his experience. He gave his consent for us to share his story and the photographs of the arm.

Shedding of genital herpes simplex virus was frequent soon after first-time infection but declined significantly during the first year, based on data from 82 individuals.

Genital herpes simplex virus (HSV) infections remain common and incurable; consequently, the population with residual infection continues to rise, Christine Johnston, MD, of the University of Washington, Seattle, and colleagues wrote. However, data on the viral shedding trajectory of genital HSV-1 are limited, although HSV-1 accounts for an increasing number of infections.

In a study published in JAMA the researchers recruited 82 women with first-episode genital HSV-1 infections from sexual health and primary care clinics in Seattle, between 2013 and 2018. The participants supplied self-collected oral and genital swabs for daily HSV polymerase chain reaction testing for two 30-day periods at 2 months and 11 months after their initial symptoms. The study population was not pregnant and did not have HIV infection. The median age of the participants was 26 years, 54 were women, and 42 had primary HSV-1 infections. Primary HSV-1 infection was defined as the lack of HSV antibody at baseline or an evolving antibody profile, based on the University of Washington HSV Western Blot.

The primary outcome was the rates of genital and oral HSV shedding and lesions at 2 and 11 months and up to 2 years after an initial HSV-1 infection.

At 2 months, approximately two-thirds (64.6%) of the participants had HSV-1 in the genital tract and 29.3% had virus in the mouth. Genital shedding of HSV-1 was detected in 12.1% of 2,264 total testing days at 2 months, but this rate declined to 7.1% of 1,719 testing days at 11 months (relative risk, 0.52).

The researchers identified oral HSV-1 shedding on 3.9% of 2,247 testing days at 2 months, with a slight increase to 5.1% of 1,714 testing days at 11 months.

Both genital and oral lesions were rare, with reports of 2.6% and 0.4%, respectively, at 2 months and 3.8% and 0.5%, respectively, at 11 months.

The risk of genital shedding was significantly higher in individuals with primary HSV-1, compared with those with nonprimary infections (7.9% vs. 2.9%; RR, 2.75). The overall rate of genital shedding was 17.2% for those with primary HSV-1, of which 15.2% was asymptomatic. Oral shedding was similar for individuals with primary and nonprimary HSV in a multivariate analysis.

In addition, HSV-specific CD4+ and CD8+ T-cell responses were identified in all participants, and these remained stable during the study period. No association appeared between rates of genital and oral shedding and the proportion of cells that expressed two, three, or four cytokines.

The current study is the first known to comprehensively assess genital and oral HSV-1 viral shedding using polymerase chain reaction, the researchers wrote. “Characterizing shedding rates is clinically important because patients with genital herpes are often concerned about transmission to sexual partners, which usually occurs in the absence of lesions.”

The study findings were limited by several factors including the 22% loss of participants to follow-up by the end of the first year, and the use of data from a single location with a primarily White population, the researchers noted. Another limitation was reliance on self-reports and the potential underestimation of recurrences because of the possible use of antiviral medications between swabbing periods.

However, the results indicate the early frequency of HSV-1 shedding and suggest that suppressive therapy might benefit individuals with primary HSV-1 during their first year of infection, the researchers said.
 

Findings may improve HSV management

The current study helps fill a knowledge gap regarding the natural history of genital HSV-1 infections, Richard J. Whitley, MD, and Edward W. Hook III, MD, both of the University of Alabama at Birmingham, wrote in an accompanying editorial. Despite the small study population, the data represent the largest cohort to date of individuals with first-episode infection and up to 2 years’ follow-up.

Although HSV-2 shedding is greater and associated with more symptoms, seroprevalence of HSV-2 in the United States is declining, they noted. Therefore, the findings can inform patient counseling and recommendations for antiviral therapy that may extend to managing HSV-1 in pregnant women as well, although no pregnant women were included in the study.

“For clinicians, these data emphasize the importance of determining the HSV viral type in persons presenting with initial episodes of genital herpes to accurately counsel patients regarding risk of clinical recurrence, the likelihood of asymptomatic shedding of virus and hence transmission, and antiviral prophylaxis,” the editorialists emphasized. For investigators, the results should prompt additional studies of the host defense against HSV and improved serological testing.
 

Study supports need for attention to HSV-1

“Genital herpes is an extremely common sexually transmitted infection, and often only HSV-2 is measured,” Sarah W. Prager, MD, of the University of Washington, Seattle, said in an interview. “This study shows that HSV-1 also accounts for a significant amount of genital disease, and should also be considered when determining prevalence of genital herpes.

“I was not surprised to see that viral shedding decreased significantly over the first year after diagnosis, and similarly not surprised that lesions were rare after the initial infection,” said Dr. Prager, who was not involved in the study. “I was somewhat surprised to see that genital HSV-1 shedding was more common than oral shedding.”

Dr. Prager said that she would advise clinicians against serum HSV testing unless someone has an active genital lesion. “Testing after a lesion will often reveal HSV-1, and patients should be counseled that shedding will decrease over the first year. Subsequent genital lesions are uncommon, but certainly possible, and oral lesions and shedding are both rare.” ]

More research is needed in a more diverse population, Dr. Prager emphasized. Following patients for more than a year and learning more about the use of antiviral medications also would be useful.

The study was supported in part by the National Institutes of Health/National Institute of Allergy and Infectious Diseases through grants to several authors, including lead author Dr. Johnston. Dr. Johnston also disclosed personal fees from AbbVie, grants from Gilead, royalties from UpToDate, and personal fees from GlaxoSmithKline unrelated to the current study. Dr. Whitley disclosed personal fees from Virios Therapeutics as a board member and shareholder during the conduct of the study, royalties from Aettis unrelated to the submitted work, and serving on an advisory board for Visby Diagnostics. Dr. Hook disclosed serving on an advisory board for Visby Diagnostics unrelated to the submitted work. Dr. Prager had no conflicts to disclose and serves on the editorial advisory board of Ob.Gyn News.
 

Shedding of genital herpes simplex virus was frequent soon after first-time infection but declined significantly during the first year, based on data from 82 individuals.

Genital herpes simplex virus (HSV) infections remain common and incurable; consequently, the population with residual infection continues to rise, Christine Johnston, MD, of the University of Washington, Seattle, and colleagues wrote. However, data on the viral shedding trajectory of genital HSV-1 are limited, although HSV-1 accounts for an increasing number of infections.

In a study published in JAMA the researchers recruited 82 women with first-episode genital HSV-1 infections from sexual health and primary care clinics in Seattle, between 2013 and 2018. The participants supplied self-collected oral and genital swabs for daily HSV polymerase chain reaction testing for two 30-day periods at 2 months and 11 months after their initial symptoms. The study population was not pregnant and did not have HIV infection. The median age of the participants was 26 years, 54 were women, and 42 had primary HSV-1 infections. Primary HSV-1 infection was defined as the lack of HSV antibody at baseline or an evolving antibody profile, based on the University of Washington HSV Western Blot.

The primary outcome was the rates of genital and oral HSV shedding and lesions at 2 and 11 months and up to 2 years after an initial HSV-1 infection.

At 2 months, approximately two-thirds (64.6%) of the participants had HSV-1 in the genital tract and 29.3% had virus in the mouth. Genital shedding of HSV-1 was detected in 12.1% of 2,264 total testing days at 2 months, but this rate declined to 7.1% of 1,719 testing days at 11 months (relative risk, 0.52).

The researchers identified oral HSV-1 shedding on 3.9% of 2,247 testing days at 2 months, with a slight increase to 5.1% of 1,714 testing days at 11 months.

Both genital and oral lesions were rare, with reports of 2.6% and 0.4%, respectively, at 2 months and 3.8% and 0.5%, respectively, at 11 months.

The risk of genital shedding was significantly higher in individuals with primary HSV-1, compared with those with nonprimary infections (7.9% vs. 2.9%; RR, 2.75). The overall rate of genital shedding was 17.2% for those with primary HSV-1, of which 15.2% was asymptomatic. Oral shedding was similar for individuals with primary and nonprimary HSV in a multivariate analysis.

In addition, HSV-specific CD4+ and CD8+ T-cell responses were identified in all participants, and these remained stable during the study period. No association appeared between rates of genital and oral shedding and the proportion of cells that expressed two, three, or four cytokines.

The current study is the first known to comprehensively assess genital and oral HSV-1 viral shedding using polymerase chain reaction, the researchers wrote. “Characterizing shedding rates is clinically important because patients with genital herpes are often concerned about transmission to sexual partners, which usually occurs in the absence of lesions.”

The study findings were limited by several factors including the 22% loss of participants to follow-up by the end of the first year, and the use of data from a single location with a primarily White population, the researchers noted. Another limitation was reliance on self-reports and the potential underestimation of recurrences because of the possible use of antiviral medications between swabbing periods.

However, the results indicate the early frequency of HSV-1 shedding and suggest that suppressive therapy might benefit individuals with primary HSV-1 during their first year of infection, the researchers said.
 

Findings may improve HSV management

The current study helps fill a knowledge gap regarding the natural history of genital HSV-1 infections, Richard J. Whitley, MD, and Edward W. Hook III, MD, both of the University of Alabama at Birmingham, wrote in an accompanying editorial. Despite the small study population, the data represent the largest cohort to date of individuals with first-episode infection and up to 2 years’ follow-up.

Although HSV-2 shedding is greater and associated with more symptoms, seroprevalence of HSV-2 in the United States is declining, they noted. Therefore, the findings can inform patient counseling and recommendations for antiviral therapy that may extend to managing HSV-1 in pregnant women as well, although no pregnant women were included in the study.

“For clinicians, these data emphasize the importance of determining the HSV viral type in persons presenting with initial episodes of genital herpes to accurately counsel patients regarding risk of clinical recurrence, the likelihood of asymptomatic shedding of virus and hence transmission, and antiviral prophylaxis,” the editorialists emphasized. For investigators, the results should prompt additional studies of the host defense against HSV and improved serological testing.
 

Study supports need for attention to HSV-1

“Genital herpes is an extremely common sexually transmitted infection, and often only HSV-2 is measured,” Sarah W. Prager, MD, of the University of Washington, Seattle, said in an interview. “This study shows that HSV-1 also accounts for a significant amount of genital disease, and should also be considered when determining prevalence of genital herpes.

“I was not surprised to see that viral shedding decreased significantly over the first year after diagnosis, and similarly not surprised that lesions were rare after the initial infection,” said Dr. Prager, who was not involved in the study. “I was somewhat surprised to see that genital HSV-1 shedding was more common than oral shedding.”

Dr. Prager said that she would advise clinicians against serum HSV testing unless someone has an active genital lesion. “Testing after a lesion will often reveal HSV-1, and patients should be counseled that shedding will decrease over the first year. Subsequent genital lesions are uncommon, but certainly possible, and oral lesions and shedding are both rare.” ]

More research is needed in a more diverse population, Dr. Prager emphasized. Following patients for more than a year and learning more about the use of antiviral medications also would be useful.

The study was supported in part by the National Institutes of Health/National Institute of Allergy and Infectious Diseases through grants to several authors, including lead author Dr. Johnston. Dr. Johnston also disclosed personal fees from AbbVie, grants from Gilead, royalties from UpToDate, and personal fees from GlaxoSmithKline unrelated to the current study. Dr. Whitley disclosed personal fees from Virios Therapeutics as a board member and shareholder during the conduct of the study, royalties from Aettis unrelated to the submitted work, and serving on an advisory board for Visby Diagnostics. Dr. Hook disclosed serving on an advisory board for Visby Diagnostics unrelated to the submitted work. Dr. Prager had no conflicts to disclose and serves on the editorial advisory board of Ob.Gyn News.
 

Shedding of genital herpes simplex virus was frequent soon after first-time infection but declined significantly during the first year, based on data from 82 individuals.

Genital herpes simplex virus (HSV) infections remain common and incurable; consequently, the population with residual infection continues to rise, Christine Johnston, MD, of the University of Washington, Seattle, and colleagues wrote. However, data on the viral shedding trajectory of genital HSV-1 are limited, although HSV-1 accounts for an increasing number of infections.

In a study published in JAMA the researchers recruited 82 women with first-episode genital HSV-1 infections from sexual health and primary care clinics in Seattle, between 2013 and 2018. The participants supplied self-collected oral and genital swabs for daily HSV polymerase chain reaction testing for two 30-day periods at 2 months and 11 months after their initial symptoms. The study population was not pregnant and did not have HIV infection. The median age of the participants was 26 years, 54 were women, and 42 had primary HSV-1 infections. Primary HSV-1 infection was defined as the lack of HSV antibody at baseline or an evolving antibody profile, based on the University of Washington HSV Western Blot.

The primary outcome was the rates of genital and oral HSV shedding and lesions at 2 and 11 months and up to 2 years after an initial HSV-1 infection.

At 2 months, approximately two-thirds (64.6%) of the participants had HSV-1 in the genital tract and 29.3% had virus in the mouth. Genital shedding of HSV-1 was detected in 12.1% of 2,264 total testing days at 2 months, but this rate declined to 7.1% of 1,719 testing days at 11 months (relative risk, 0.52).

The researchers identified oral HSV-1 shedding on 3.9% of 2,247 testing days at 2 months, with a slight increase to 5.1% of 1,714 testing days at 11 months.

Both genital and oral lesions were rare, with reports of 2.6% and 0.4%, respectively, at 2 months and 3.8% and 0.5%, respectively, at 11 months.

The risk of genital shedding was significantly higher in individuals with primary HSV-1, compared with those with nonprimary infections (7.9% vs. 2.9%; RR, 2.75). The overall rate of genital shedding was 17.2% for those with primary HSV-1, of which 15.2% was asymptomatic. Oral shedding was similar for individuals with primary and nonprimary HSV in a multivariate analysis.

In addition, HSV-specific CD4+ and CD8+ T-cell responses were identified in all participants, and these remained stable during the study period. No association appeared between rates of genital and oral shedding and the proportion of cells that expressed two, three, or four cytokines.

The current study is the first known to comprehensively assess genital and oral HSV-1 viral shedding using polymerase chain reaction, the researchers wrote. “Characterizing shedding rates is clinically important because patients with genital herpes are often concerned about transmission to sexual partners, which usually occurs in the absence of lesions.”

The study findings were limited by several factors including the 22% loss of participants to follow-up by the end of the first year, and the use of data from a single location with a primarily White population, the researchers noted. Another limitation was reliance on self-reports and the potential underestimation of recurrences because of the possible use of antiviral medications between swabbing periods.

However, the results indicate the early frequency of HSV-1 shedding and suggest that suppressive therapy might benefit individuals with primary HSV-1 during their first year of infection, the researchers said.
 

Findings may improve HSV management

The current study helps fill a knowledge gap regarding the natural history of genital HSV-1 infections, Richard J. Whitley, MD, and Edward W. Hook III, MD, both of the University of Alabama at Birmingham, wrote in an accompanying editorial. Despite the small study population, the data represent the largest cohort to date of individuals with first-episode infection and up to 2 years’ follow-up.

Although HSV-2 shedding is greater and associated with more symptoms, seroprevalence of HSV-2 in the United States is declining, they noted. Therefore, the findings can inform patient counseling and recommendations for antiviral therapy that may extend to managing HSV-1 in pregnant women as well, although no pregnant women were included in the study.

“For clinicians, these data emphasize the importance of determining the HSV viral type in persons presenting with initial episodes of genital herpes to accurately counsel patients regarding risk of clinical recurrence, the likelihood of asymptomatic shedding of virus and hence transmission, and antiviral prophylaxis,” the editorialists emphasized. For investigators, the results should prompt additional studies of the host defense against HSV and improved serological testing.
 

Study supports need for attention to HSV-1

“Genital herpes is an extremely common sexually transmitted infection, and often only HSV-2 is measured,” Sarah W. Prager, MD, of the University of Washington, Seattle, said in an interview. “This study shows that HSV-1 also accounts for a significant amount of genital disease, and should also be considered when determining prevalence of genital herpes.

“I was not surprised to see that viral shedding decreased significantly over the first year after diagnosis, and similarly not surprised that lesions were rare after the initial infection,” said Dr. Prager, who was not involved in the study. “I was somewhat surprised to see that genital HSV-1 shedding was more common than oral shedding.”

Dr. Prager said that she would advise clinicians against serum HSV testing unless someone has an active genital lesion. “Testing after a lesion will often reveal HSV-1, and patients should be counseled that shedding will decrease over the first year. Subsequent genital lesions are uncommon, but certainly possible, and oral lesions and shedding are both rare.” ]

More research is needed in a more diverse population, Dr. Prager emphasized. Following patients for more than a year and learning more about the use of antiviral medications also would be useful.

The study was supported in part by the National Institutes of Health/National Institute of Allergy and Infectious Diseases through grants to several authors, including lead author Dr. Johnston. Dr. Johnston also disclosed personal fees from AbbVie, grants from Gilead, royalties from UpToDate, and personal fees from GlaxoSmithKline unrelated to the current study. Dr. Whitley disclosed personal fees from Virios Therapeutics as a board member and shareholder during the conduct of the study, royalties from Aettis unrelated to the submitted work, and serving on an advisory board for Visby Diagnostics. Dr. Hook disclosed serving on an advisory board for Visby Diagnostics unrelated to the submitted work. Dr. Prager had no conflicts to disclose and serves on the editorial advisory board of Ob.Gyn News.